Cell Biology | DNA Structure & Organization 🧬 — Transcript

Full transcript

1. 0:14what's up ninja nerds in this video
2. 0:15today we're going to be talking about
3. 0:16the structure of dna but before we get
4. 0:18started please continue to support us
5. 0:20by hitting that like button commenting
6. 0:21down the comment section and please
7. 0:23subscribe
8. 0:24also down in the description box we have
9. 0:25links to our facebook and instagram as
10. 0:27well as our patreon you guys want to go
11. 0:28to our patreon
12. 0:29we'll have supplemental resources there
13. 0:31that help engage you
14. 0:33more in this learning process all right
15. 0:35engineers let's get into it
16. 0:37all right ninja nurse when we start
17. 0:38talking about the structure of dna
18. 0:40before we do that we have to have a nice
19. 0:41little conversation about the nucleus
20. 0:43because that's where dna is housed
21. 0:44so let's have a quick little dive into
22. 0:46the structure of the nucleus
23. 0:48what are the components within the
24. 0:49nucleus and what are the basic functions
25. 0:51of what they do
26. 0:52first thing is here here's we see the
27. 0:53nucleus and you have this blue structure
28. 0:56a double membrane kind of structure it's
29. 0:57a phospholipid bilayer if you will
30. 1:00and this phospholipid bilayer is
31. 1:01referred to as your
32. 1:03nuclear envelope and we'll go over all
33. 1:05the different components of that
34. 1:07okay the next thing is within the
35. 1:09nuclear envelope you have these little
36. 1:10proteins
37. 1:12that are nuclear kind of core complex
38. 1:14that allow for
39. 1:15certain things to be able to move to and
40. 1:18from the nucleus and into the cytoplasm
41. 1:20and this structure right here is very
42. 1:22important and these are called your
43. 1:23nuclear
44. 1:24pores okay and they're usually made up
45. 1:27of proteins which help with the
46. 1:29transport of things
47. 1:30to and from the actual cell cytoplasm
48. 1:33and nucleus
49. 1:34the next thing i need you guys to know
50. 1:35is inside
51. 1:37of the actual nucleus is a big component
52. 1:41of
53. 1:41a bunch of stuff and that bunch of stuff
54. 1:43that's inside of it
55. 1:44all the stuff inside is called the
56. 1:48nucleoplasm
57. 1:49and there's a couple different
58. 1:51components to the nucleoplasm
59. 1:53that we're going to go into great detail
60. 1:54in okay and this is the one that we'll
61. 1:56pretty much focus on but again
62. 1:58we have the main components here that we
63. 2:00need to know for the structure of the
64. 2:01nucleus
65. 2:03now first thing nuclear envelope
66. 2:05remember i told you that there's two
67. 2:06components there's an outer membrane and
68. 2:08an inner membrane that's the thing i
69. 2:10need you to know
70. 2:11this outer membrane this component right
71. 2:13here is what's
72. 2:14kind of having ribosomes studded around
73. 2:17the outside
74. 2:18okay so the next thing is your outer
75. 2:20membrane
76. 2:22the thing i want you to associate with
77. 2:24the outer membrane
78. 2:25is where the ribosomes will be because
79. 2:27what will happen is
80. 2:28mrna will come out of these nuclear
81. 2:30pores near the outer membrane
82. 2:32bind with a ribosome and then get
83. 2:34translated to the
84. 2:35rough endoplasmic reticulum and then
85. 2:38that's where translation
86. 2:39protein synthesis will occur the next
87. 2:41thing is the inner membrane
88. 2:43the inner membrane is very important and
89. 2:45there's a particular
90. 2:46pathology that can be involved with the
91. 2:48inner membrane that i want you guys to
92. 2:50know for your usmles
93. 2:52and what is that the inner membrane
94. 2:54contains a very important protein i want
95. 2:56to draw this one out here in pink
96. 2:57because of this pink filamentous protein
97. 2:59that's on the inside
98. 3:00this inner membrane kind of provides a
99. 3:02structural framework for the
100. 3:04actual nucleus and allows for
101. 3:05interaction with chromatin where genes
102. 3:07are expressed
103. 3:08and also undergo replication and this
104. 3:11protein is called
105. 3:12lamins there's lamin proteins and why
106. 3:15you guys need to know this that there's
107. 3:16a mutation within a particular type of
108. 3:19lamin called lamin a
109. 3:21and what happens is if it's absent it
110. 3:23causes individuals patients who
111. 3:26have this disease to age very very
112. 3:28quickly and it's called progeria
113. 3:30okay the next thing is your nuclear
114. 3:33pores your nuclear pores are very
115. 3:34straightforward
116. 3:35what do they do they allow for things to
117. 3:37move out of the nucleus into the
118. 3:39cytoplasm
119. 3:40and from the cytoplasm into the nucleus
120. 3:43what would we need for that just give me
121. 3:45one quick example
122. 3:46of something that would be going out via
123. 3:49the nuclear pores
124. 3:50really quick one mrna mrna would be one
125. 3:53that's kind of
126. 3:54leaving the nucleus
127. 3:57because we need this mrna to
128. 4:00go out into the cytoplasm and get
129. 4:02translated by the ribosomes
130. 4:04all right so give me an example of
131. 4:05something coming in to the nucleus what
132. 4:07do we need to make dna that's a perfect
133. 4:10example
134. 4:10you know you synthesize nucleotides
135. 4:12within different areas of the cell
136. 4:14what if i bring in nucleotides that
137. 4:17could be a very simple reason of why
138. 4:19i need this little transport protein or
139. 4:21nuclear pores to move things
140. 4:23in and out of the nucleus really simple
141. 4:24example right it's meant to be basic
142. 4:27the next thing is the nucleoplasm in the
143. 4:29nucleoplasm there's two primary things
144. 4:31that i want you guys to know
145. 4:33the first one here we're going to color
146. 4:35coordinate is this big circular like
147. 4:37little chex mix looking thing this thing
148. 4:39is called
149. 4:41your nucleolus this is one of the
150. 4:42components of the nucleoplasm
151. 4:45what i want you to know is in the
152. 4:46nucleolus this is where
153. 4:49your r rna synthesis occurs
154. 4:52so you have some dna in the area of the
155. 4:55nucleolus
156. 4:56and what's happening is it is getting
157. 4:58transcribed to making rrna
158. 5:00also you're making some subunits
159. 5:04some ribosomal subunits and the reason
160. 5:06why is
161. 5:07when you make rrna which is a nucleic
162. 5:10acid and you make subunits
163. 5:12which are your proteins and there's
164. 5:13different types of subunits
165. 5:15there's a large ribosomal subunit and a
166. 5:17small ribosomal subunit
167. 5:18the combination of these two is what
168. 5:21gives you
169. 5:22your ribosomes okay and that's what i
170. 5:24want you guys to remember
171. 5:26so what i tell you guys is that in the
172. 5:27nucleolus what is happening there
173. 5:29ribosomal synthesis you know what's
174. 5:31actually really interesting ribosomes
175. 5:33are
176. 5:33just small enough that they can fit
177. 5:36through the nuclear pore
178. 5:37okay and so that also is another thing
179. 5:39that can be shuttled out all right so
180. 5:41the next component of the nucleoplasm
181. 5:43is your chromatin and this is what i
182. 5:45really want us to focus on because this
183. 5:46is where dna is
184. 5:48so chromatin i need you to remember that
185. 5:50this is made up of two different things
186. 5:51that we'll discuss in a little bit more
187. 5:52detail
188. 5:53one is what's called histone proteins
189. 5:57okay these are very important and the
190. 5:59other one is your good old
191. 6:00dna now these two combos are what make
192. 6:04chromatin but chromatin is also a little
193. 6:06bit special
194. 6:07and we'll talk about how but histones
195. 6:09and dna
196. 6:10their combination works in a particular
197. 6:13way
198. 6:14because of their positive negative
199. 6:15attraction that it condenses dna
200. 6:18into really really compact structures
201. 6:20that can fit within a nucleus in
202. 6:22our in our cells dna is really long
203. 6:25and if i can condense it i can fit a
204. 6:27bunch of dna inside of my nuclei
205. 6:30so what happens is chromatin
206. 6:33can get condensed down into two forms
207. 6:36one of the forms is the highly condensed
208. 6:39h highly condensed i want you to
209. 6:41remember heterochromatin
210. 6:44heterochromatin what i want you to
211. 6:46associate this with
212. 6:47highly condensed in other words this is
213. 6:51so condensed
214. 6:52where the histones in the dna have such
215. 6:54a strong attraction with one another
216. 6:56that it's really hard for little enzymes
217. 6:58to get in there transcribe the dna and
218. 7:00make
219. 7:00rna so what would happen with this there
220. 7:03would be
221. 7:04no transcription
222. 7:07in this type of chromatin
223. 7:10very very important very high yield the
224. 7:13next thing is
225. 7:14there's another type of chromatin but
226. 7:16this one is u-chromatin
227. 7:18and remember that e it's expressed
228. 7:22so this is a loose chromatin and i like
229. 7:26to remember
230. 7:26e for expressing what does that mean
231. 7:29it's expressing
232. 7:30it's there's a weak attraction
233. 7:33there's a relaxed kind of relaxed
234. 7:35attraction between the histones
235. 7:37and the dna and because of that there's
236. 7:40nice space where the
237. 7:41dna the rna polymerases can get in there
238. 7:44and make rna
239. 7:45and so this occurs because
240. 7:49we want this portion of the dna to be
241. 7:51able to
242. 7:52undergo transcription so again big
243. 7:55difference between hetero is highly
244. 7:56condensed
245. 7:57does not undergo transcription
246. 7:58euchromatin is loose chromatin or
247. 8:01expressing chromatin
248. 8:03meaning that you can transcribe it and
249. 8:05make rna
250. 8:06get it very important okay
251. 8:10the last thing i want you guys to know
252. 8:11is that chromatin whenever our cells are
253. 8:13undergoing a lot of replication
254. 8:15they want to allow for that chromatin to
255. 8:17get passed on to the daughter cell so
256. 8:19your parent cell has to pass on the
257. 8:21dna to daughter cells and so the way it
258. 8:24does that
259. 8:24is the chromatin during cell replication
260. 8:28it condenses down into
261. 8:31what's called chromosomes
262. 8:35and that is where i want us to kind of
263. 8:37take a quick little second here and
264. 8:39understand
265. 8:40dna a little bit more is looking at how
266. 8:43chromosomes a really condensed structure
267. 8:46of chromatin contains loops and loops in
268. 8:50loops of dna wrapped around histone
269. 8:52proteins and what's the significance of
270. 8:54that
271. 8:54let's move on to that part all right so
272. 8:56we talked about how chromatin is made up
273. 8:57of dna histone proteins
274. 8:59and whenever the cells are starting to
275. 9:00replicate they need to condense their
276. 9:02chromatin down so that they can easily
277. 9:03pass their genetic material onto the
278. 9:05daughter cells so what i want you to
279. 9:07recognize is this right here
280. 9:08is our chromosome and what i want us to
281. 9:11do is i want to yank
282. 9:13all of that chromatin out of the
283. 9:15chromosome
284. 9:16and look at it deeper and deeper to the
285. 9:19microscopic
286. 9:20level okay so once i take my chromosome
287. 9:23i'm going to start
288. 9:24yanking some of the dna out of this as i
289. 9:26yank some of the dna out it kind of
290. 9:28comes out in this loopy kind of
291. 9:30continuous fiber so
292. 9:31i have my chromosome i yank some of it
293. 9:33out and then i get this
294. 9:35loopy kind of continuous fiber that
295. 9:37you're going to see here
296. 9:40after i continue to keep kind of going a
297. 9:42little bit and i
298. 9:43keep getting into the smaller and
299. 9:45smaller versions of it as i'm looking
300. 9:46deeper into the structure
301. 9:48then it starts to get tight helical
302. 9:51fibers
303. 9:53okay so we get tight helical fibers so
304. 9:57we got loopy continuous fibers
305. 9:58tight helical fibers and then what
306. 10:00happens is you can't really see it that
307. 10:01well but they're in there i'm going to
308. 10:03draw some little red
309. 10:04circles and little red dots in there you
310. 10:06start seeing these red structures
311. 10:08that the dna is kind of wrapping around
312. 10:11and that's where we got to zoom in on
313. 10:13them you see this red structure here
314. 10:15where dna is wrapping around it what did
315. 10:17i tell you chromatin was made up of
316. 10:19dna and histone proteins let's take a
317. 10:21quick second to understand the
318. 10:23significance of this
319. 10:24so now we're going to take and zoom in
320. 10:26on this little structure here because
321. 10:28there's a significance that we need to
322. 10:30kind of talk about a little bit
323. 10:31so we know that dna is wrapped around
324. 10:33this kind of big or reddish structure
325. 10:35what is that so here's our dna we're
326. 10:37kind of zooming in on it
327. 10:38and then the next component is this red
328. 10:40structure here and this is a histone
329. 10:43kind of octamer what the heck is an
330. 10:46octomer
331. 10:46so octomers you know there's eight
332. 10:49there's eight of something
333. 10:50and there's particular histone proteins
334. 10:52and i and it's really quick that i want
335. 10:53you guys to know this
336. 10:54there's what's called h2a
337. 10:58h2b h3
338. 11:02and h4 and so if you count these up
339. 11:06right there's four of these so what do i
340. 11:08have to have double of everything
341. 11:10to make an octamer so i'm going to have
342. 11:12two of each one of these things
343. 11:14and the combination of all of these two
344. 11:16four six eight
345. 11:18these components the h2a h2b h3h4
346. 11:21they make up an octamer and all of these
347. 11:24h's
348. 11:24are histones okay they're proteins what
349. 11:28i really need you to focus on with this
350. 11:30histones have particular amino acids
351. 11:34called lysine and arginine
352. 11:40and the significance of these is that
353. 11:42lysine and arginine
354. 11:43are positively charged amino acids
355. 11:47very important that you guys remember
356. 11:48that okay
357. 11:50why because dna and we'll talk about
358. 11:52what is
359. 11:53making dna negative a little bit later
360. 11:55but dna
361. 11:56has a negative charge so dna has i'll
362. 12:00tell you quick
363. 12:00it's phosphate groups within the dna
364. 12:02that creates a negative charge
365. 12:04so these histone proteins they all have
366. 12:06positive charges
367. 12:08and so because they have all these
368. 12:10positive charges around them
369. 12:11what happens to opposite charges they
370. 12:14attract one another
371. 12:15so then the lysine and arginine on the
372. 12:17histones will interact with the
373. 12:18phosphate groups on dna and tightly
374. 12:20compact with one another
375. 12:21and that's what allows the dna to get
376. 12:23really nice and condensed
377. 12:25that is why i really need you guys to
378. 12:26know that there's a particular name
379. 12:30for whenever the dna wraps twice around
380. 12:33this
381. 12:33octamer of histone proteins you know
382. 12:35what this is called we call this a
383. 12:37nucleosome
384. 12:38so we call this a nucleosome
385. 12:42why am i spending some time mentioning
386. 12:44the significance of the nucleosome
387. 12:46and these histone proteins i'll tell you
388. 12:48why the reason why is
389. 12:51histone proteins in dna can be modified
390. 12:54via the process of epigenetics we're not
391. 12:55going to get into a lot of detail on
392. 12:56that
393. 12:57but i want to just quickly brush over
394. 12:59this because there is pertinence to this
395. 13:00for your usmles
396. 13:01so there's concepts of what's called
397. 13:03epigenetics where you control or
398. 13:06regulate the expression of genes
399. 13:08throughout
400. 13:09you know the lifetime from parental to
401. 13:11daughter cells and
402. 13:12and and so on and so forth and how we do
403. 13:15this
404. 13:16is by we modify the activity of the
405. 13:19interaction between dna and histone
406. 13:21proteins
407. 13:21and how do we do that well one of the
408. 13:23things that we can do is we can modify
409. 13:25the dna okay and we'll talk about this
410. 13:28one
411. 13:29and the next thing that we can do is
412. 13:31besides modifying dna
413. 13:32is we can modify histone proteins and
414. 13:35this is the one that's a little bit more
415. 13:37significant
416. 13:39with modifying dna within dna there's a
417. 13:42specific thing that you can do let's say
418. 13:44here i have a quick
419. 13:45strand of dna and in the dna there's
420. 13:48particular nucleotides called cytosine
421. 13:50and guanine
422. 13:52these are located in these areas here
423. 13:54we're going to put cgcgcg
424. 13:58these areas where there's a lot of
425. 13:59cytosine and guanine are called cpg
426. 14:01islands
427. 14:02and what happens is we can use different
428. 14:04types of enzymes
429. 14:06and what these enzymes do is they add
430. 14:09methyl groups
431. 14:10onto wherever these cytosine and guanine
432. 14:13areas are
433. 14:14you know what that does whenever you add
434. 14:15methyl groups onto these cpg
435. 14:17islands it basically
436. 14:20inhibits this area of dna from being
437. 14:23able to
438. 14:24be expressed if you can't express a
439. 14:26particular part of dna can you
440. 14:28transcribe it
441. 14:29make rna and then make proteins no
442. 14:32that is important so what i want you to
443. 14:34remember is epigenetically
444. 14:35we can modify the dna by methylating
445. 14:38what's called what are these little
446. 14:40things here called we call them
447. 14:42cpg islands areas of
448. 14:45lots of cytosine and guanine we
449. 14:47methylate them and what is the response
450. 14:49to this
451. 14:51this inhibits gene
452. 14:56transcription very important so that's
453. 14:59one way that we can control
454. 15:00which genes we want to be expressed in
455. 15:02particular cells and our liver cell
456. 15:04we're going to make a particular protein
457. 15:06and the other cell like in our brain we
458. 15:07might not want to make that particular
459. 15:09protein
460. 15:10if we methylate that gene that's what
461. 15:11determines the differences
462. 15:13pretty makes sense right same thing with
463. 15:16the histone proteins
464. 15:18if we take for example those histone
465. 15:19proteins and we actually kind of wrap
466. 15:21some dna around it
467. 15:23here i'm going to have a histone
468. 15:24proteins like this
469. 15:26dna here and then inside of this is
470. 15:28going to be your histone proteins
471. 15:30okay right now the histone proteins in
472. 15:33the dna are really tightly interacted
473. 15:35with one another
474. 15:36not a chance and heck a little enzyme
475. 15:39can get
476. 15:40in there and transcribe the dna there
477. 15:42where that
478. 15:43histone protein is occupying so
479. 15:46what i can do is is i can use special
480. 15:49little enzymes
481. 15:51and what these enzymes do is they add on
482. 15:54what's called an acetyl group
483. 15:56okay they can add on an acetyl group and
484. 15:59when i add on the acetyl group it does
485. 16:01something very very interesting what
486. 16:03does it do
487. 16:03let me show you it takes this
488. 16:06interaction between the dna and the
489. 16:07histone proteins
490. 16:09and makes it really lax
491. 16:12okay we'll leave this one alone because
492. 16:14we're going to talk about that in a
493. 16:14second but
494. 16:15now look the histone protein between the
495. 16:19dna there's a lot more space
496. 16:21if there's a lot of space now what can
497. 16:24happen
498. 16:26i can now have my little rna polymerase
499. 16:28enzyme get in there
500. 16:29and transcribe that portion of the dna
501. 16:32so this can be transcribe so
502. 16:36transcription can occur here
503. 16:42now let's say i take another situation
504. 16:45where instead i'm going to
505. 16:48put a methyl group on that histone
506. 16:50protein okay
507. 16:51so now what i'm going to do is i'm going
508. 16:52to put a methyl group onto that histone
509. 16:54protein
510. 16:55now here's the thing that's interesting
511. 16:58if i only add in one methyl group
512. 17:02just one methyl group okay we'll put
513. 17:05that here
514. 17:06it can perform the same type of effect
515. 17:09as acetylation just one so what i'm
516. 17:12going to do is i'm just going to put
517. 17:13one methyl group here it can perform the
518. 17:16same type of action as
519. 17:18acetylation where it can relax the
520. 17:20interaction between the dna and the
521. 17:22histone proteins
522. 17:23allowing for transcription but
523. 17:26if instead i add on
524. 17:30two to three of these actual histone
525. 17:33proteins then what's gonna happen
526. 17:36i'm gonna really tighten up the
527. 17:38interaction between
528. 17:40the dna and the histone proteins there's
529. 17:42not a chance and heck
530. 17:44that the rna polymerase can get in there
531. 17:47and transcribe the dna
532. 17:48so remember if i add two to three
533. 17:51methyl groups what's going to happen
534. 17:54it's going to repress
535. 17:55gene transcription inhibit the gene from
536. 17:58being
537. 17:58transcribed making rna proteins so on
538. 18:02and so forth
539. 18:02so the result of this is you inhibit
540. 18:08transcription the last thing i want to
541. 18:11mention here
542. 18:12is that you can get the same kind of
543. 18:15effect
544. 18:16with this high amounts of methyl groups
545. 18:18that you're adding on if what if i just
546. 18:20took and i used a particular enzyme okay
547. 18:23well i have what's called a
548. 18:24a d acetylase
549. 18:30and what i did is i had this dsc lace
550. 18:33inhibit or remove
551. 18:34the acetyl group if i remove the acetyl
552. 18:37group what happens
553. 18:38am i going to allow for relaxation of
554. 18:40the dna and the histone proteins
555. 18:42no they're going to be tightly compacted
556. 18:44with one another
557. 18:45are we going to be able to transcribe
558. 18:46that gene and make rna no
559. 18:48so in quick summary if i add acetyl
560. 18:51groups to the histone proteins what does
561. 18:52it do
562. 18:53relaxes the dna and histone proteins you
563. 18:55relax it can you occur with
564. 18:56can gene transcription occur yes
565. 18:59i add one methyl group onto the histone
566. 19:01protein what does it do
567. 19:03it relaxes the histone from the dna can
568. 19:05you transcribe it
569. 19:06yes i add two to three methyl groups to
570. 19:09the histone proteins
571. 19:10what does it do it tightens up or
572. 19:13condenses
573. 19:14the interaction between the dna and the
574. 19:16histone proteins can you transcribe it
575. 19:18no last thing here is i take a d
576. 19:20acetylase enzyme
577. 19:22remove off the acetyl group now what's
578. 19:25going to happen with the dna and the
579. 19:26histone proteins is there going to be a
580. 19:28loose interaction
581. 19:28no there'll be a tight interaction and
582. 19:31what happens
583. 19:32transcription is inhibited this is
584. 19:33really important i really need you guys
585. 19:35to remember this stuff okay
586. 19:37that covers our kind of epigenetic
587. 19:38aspect of this now let's get back over
588. 19:40here one quick thing before we move into
589. 19:42the
590. 19:43kind of the really small units of dna as
591. 19:46there's one more histone protein you're
592. 19:47like dang it
593. 19:48another one you see this brown one here
594. 19:51this brown histone protein is actually
595. 19:53probably one of the most important
596. 19:54histone proteins
597. 19:56and this brown one is called h1
598. 20:00this is the h1 linker protein so this is
599. 20:02actually a linker protein
600. 20:04it links the dna nucleosomes between one
601. 20:08another
602. 20:08you see how it's doing that here's one
603. 20:10linking this nucleosome to this
604. 20:11nucleosome
605. 20:12this one to this one so it's a linker
606. 20:14protein and because it's a linker
607. 20:16protein guess what
608. 20:17it has to be the most positively charged
609. 20:20histone protein so it has the most
610. 20:23positive
611. 20:24charge associated with it so that it can
612. 20:26really condense down
613. 20:28the chromatin that's very important okay
614. 20:31now let's keep going down we've hit our
615. 20:33nucleosomes hard
616. 20:34and we've discussed how we see two wraps
617. 20:36of dna around the histone proteins
618. 20:38as we start really kind of zooming into
619. 20:40the dna around the histone proteins what
620. 20:42do we start getting
621. 20:43we start getting this kind of double
622. 20:45helix structure
623. 20:46and in this double helix structure as we
624. 20:48keep going down and down and down
625. 20:50we really start getting into the s like
626. 20:52the actual
627. 20:53microscopic components of these and what
628. 20:56are these components and this is what we
629. 20:57have to focus on which is very important
630. 20:59one is this kind of backbone here you
631. 21:01see this backbone that i'm shading in
632. 21:03blue
633. 21:04this is called your sugar phosphate
634. 21:06backbone so what is this here component
635. 21:08called
636. 21:09this is called your sugar
637. 21:12phosphate backbone and obviously as you
638. 21:15can tell it's made up of what's called a
639. 21:16ribose sugar
640. 21:17and a phosphate group and then the other
641. 21:20component is these little colorful
642. 21:22things inside
643. 21:24and these are called your nitrogenous
644. 21:27bases
645. 21:28and there's different types of
646. 21:29nitrogenous bases that we'll discuss
647. 21:32because there's there's a lot of
648. 21:33high-yield stuff associated with that
649. 21:35but the combination
650. 21:37of your sugar phosphate backbone and
651. 21:39your nitrogenous bases
652. 21:40are what makes up what's called a
653. 21:43nucleotide
654. 21:44and then a bunch of nucleotides together
655. 21:48make up a nucleic acid so when someone
656. 21:51says what is dna
657. 21:53you can just say it's a sequence of
658. 21:56nucleotides
659. 21:57that are made up of sugar phosphate and
660. 22:00nitrogenous bases
661. 22:01now let's dig into each of these
662. 22:03different constituents of dna
663. 22:05all right so the next thing i want you
664. 22:06guys to know what are the constituents
665. 22:08what makes up these nucleotides and this
666. 22:10is actually kind of the easiest
667. 22:12part thank goodness right you're like oh
668. 22:14i needed this
669. 22:16so here's what i want you guys to
670. 22:17remember easy
671. 22:19simple stuff if i have two rings what's
672. 22:22called a heterocyclic ring
673. 22:24okay two of them are representing two
674. 22:26boxes here
675. 22:27this makes up particular types of
676. 22:29nitrogenous bases
677. 22:31and these are referred to as your
678. 22:33purines
679. 22:34and there's two different types of
680. 22:36purines here one
681. 22:38is referred to as adenine
682. 22:41and the other one is referred to as
683. 22:45guanine
684. 22:49so that's the first thing i need you
685. 22:51guys to know so
686. 22:52two rings for these nitrogenous bases
687. 22:54two heterocyclic rings makes up what's
688. 22:56called your purines
689. 22:57and that's made up of adenine and
690. 22:58guanine the next thing is the red one
691. 23:01the red one if you just have one ring a
692. 23:04single ring structure
693. 23:06this makes up what's called pyrimidines
694. 23:09and your pyrimidines are made up of like
695. 23:12there's actually three
696. 23:13but we're only talking about this for
697. 23:15dna so there's actually technically
698. 23:17three pyrimidines i'll put it down but
699. 23:18i'm gonna
700. 23:19refer to it only an rna this is
701. 23:21particular to dna
702. 23:23the three types of pyrimidines you can
703. 23:24remember by cut
704. 23:26pie cut pie pyrimidines
705. 23:29remember cytosine
706. 23:33uracil and this is the only one that is
707. 23:36not in dna
708. 23:37it's only in rna all these other ones
709. 23:39are going to be in dna
710. 23:41and then thymine
711. 23:44okay these are going to be your
712. 23:46nitrogenous bases
713. 23:47and again two rings purines single ring
714. 23:50pyrimidines if you're trying to have a
715. 23:51hard time
716. 23:52separating them cut pie is going to be
717. 23:55cytosine
718. 23:55uracil thymine that makes it pyrimidines
719. 23:58the remaining two are adenine and
720. 23:59guanine
721. 24:00okay now that's one component we talked
722. 24:04about the next component is the pinto
723. 24:06sugars
724. 24:07the pinto sugars i want you to remember
725. 24:09that this is a a ring sugar
726. 24:11and usually it's in the form of what's
727. 24:12called two different types one is you
728. 24:14have what's called
729. 24:15a oxyribose but we're just going to put
730. 24:17it as ribose and the other one is called
731. 24:20deoxyribose and believe it or not
732. 24:23there's not much of a difference between
733. 24:24these
734. 24:25it's really one just atom that's
735. 24:27different
736. 24:28and what happens is you have this
737. 24:31structure here
738. 24:33that's giving you the basic structure
739. 24:35this is your basic structure here
740. 24:37at this point here this is your number
741. 24:39one kind of carbon here
742. 24:41and what happens is this is where well
743. 24:43it's actually right
744. 24:44here but what happens is this is what
745. 24:47connects to your
746. 24:48nitrogenous base this is your number two
747. 24:51carbon
748. 24:52this is your number three carbon this is
749. 24:54the number four carbon
750. 24:55this is the number five carbon it's
751. 24:57actually very important for you to
752. 24:59remember
753. 24:59primarily three and five
754. 25:02okay on the two carbon this is what
755. 25:06really makes the difference
756. 25:07in ribose there's an o h
757. 25:10and deoxyribose which we'll talk about
758. 25:12in a second there is no oh
759. 25:13it's just an h the next thing i need you
760. 25:16guys to remember here
761. 25:17is on the three carbon every three
762. 25:19carbon whether it be
763. 25:20ribose or deoxyribose there's an o h
764. 25:23group
765. 25:24on the fourth carbon nothing on the
766. 25:26fifth carbon this is where i need you to
767. 25:28remember the next structure
768. 25:29and that next structure we're going to
769. 25:30draw here in orange is going to be where
770. 25:32the phosphate group will combine on to
771. 25:35okay so that's where the phosphate group
772. 25:36is i'm just trying to give you the
773. 25:37significance of the ribose sugar
774. 25:40so three group o h five group phosphate
775. 25:43two group if it's ribose has an o h
776. 25:45group first carbon
777. 25:46has the nitrogen if it's a deoxyribose
778. 25:50it's literally the same dang structure
779. 25:52the only thing that's different is what
780. 25:55guys
781. 25:56i know you guys are yelling it out this
782. 25:57is a what
783. 25:59h there's no oh there
784. 26:03okay that's why it's oxy versus deoxy
785. 26:06right pretty straightforward on the
786. 26:08third carbon what's here oh
787. 26:10on the fourth carbon nothing ch2 which
788. 26:13is your fifth carbon what comes off of
789. 26:15that fifth carbon
790. 26:16you guys remember it is the phosphate
791. 26:19group
792. 26:20which is connected with the fifth carbon
793. 26:22okay so this is going to be
794. 26:24our ribose sugars or our pentose pentose
795. 26:27meaning it's a five
796. 26:28carbon sugar the main things i need you
797. 26:30to remember five carbon has
798. 26:31phosphate three carbon has oh group
799. 26:34difference between oxy ribose and deoxy
800. 26:36is the oh on the second carbon
801. 26:38h on the second carbon for deoxyribose
802. 26:41the next thing is the phosphate group
803. 26:44the phosphate group is really where we
804. 26:45really need to remember that this is
805. 26:46where it's the
806. 26:47negatively charged structure okay so
807. 26:49here's our phosphate group
808. 26:52okay now phosphates
809. 26:55are important because of that negative
810. 26:57charge because that's what allows for
811. 26:59the dna the negative charge of dna to
812. 27:00interact with headstone proteins
813. 27:02so what do i need you to know is just
814. 27:03this basic structure of phosphate
815. 27:05is found on what carbon first thing i
816. 27:07need to know is that it's a very
817. 27:08negatively charged
818. 27:10so that allows for that interaction with
819. 27:11dna and histones and the second thing is
820. 27:14it binds
821. 27:16to what carbon the fifth carbon
822. 27:19on the pentose sugar can't stress that
823. 27:21enough
824. 27:23all right the next thing i need you guys
825. 27:24to know is there's a couple nomenclature
826. 27:27terms that i want you guys to know
827. 27:28we're not going to go into crazy detail
828. 27:30because they can kind of be confusing we
829. 27:31talk about them more in the purine and
830. 27:33pyrimidine synthesis
831. 27:34pathways but i want you to know the
832. 27:35difference between a nucleoside
833. 27:38and a nucleotide the basic difference
834. 27:42if we just take for example i take one
835. 27:44nitrogenous base and i take one pinto
836. 27:47sugar it doesn't matter
837. 27:48that's all a nucleoside is is i'm just
838. 27:51going to have
839. 27:53this structure here
840. 27:59and my phosphate there and then what do
841. 28:01i have coming off here let's just say i
842. 28:02have
843. 28:03a period i have adenine so if i just
844. 28:06have what two structures
845. 28:08that is what makes up a nucleoside what
846. 28:09are the two components a pentose
847. 28:14sugar and what else a nitrogenous base
848. 28:19it's not technically a nucleoside this
849. 28:21is it's not not technically a nucleotide
850. 28:23it's actually a
851. 28:24nucleoside so nitrogenous base pentose
852. 28:27sugar
853. 28:28is what's called a nucleoside now a
854. 28:31nucleotide
855. 28:33is all of these things so that's where i
856. 28:35want us to finish up
857. 28:37a nucleotide is now let's build this
858. 28:38whole thing up here
859. 28:40i have my pentose sugar i have my o-h on
860. 28:43my third carbon
861. 28:44we're talking about dna so we need just
862. 28:46a deoxyribose
863. 28:48my one carbon let's just put here again
864. 28:50adenine or guanine
865. 28:51i'm putting a purine ring
866. 28:54and then again what do i have coming off
867. 28:56here on my fifth carbon
868. 28:59i have that phosphate group
869. 29:03if i have all of these things
870. 29:06what components a phosphate group a
871. 29:09pentose sugar
872. 29:10and a nitrogenous base this is what
873. 29:12makes up a nucleotide
874. 29:14we now have a basic concept of this
875. 29:17these do have different
876. 29:18names i don't want to get too bogged
877. 29:20down into that but i want you to know
878. 29:22the difference between a nucleoside
879. 29:23no phosphate nucleotide phosphate simple
880. 29:26as that
881. 29:27now that we know that let's take a bunch
882. 29:29of nucleotides
883. 29:30string them together and start making
884. 29:32our dna so now what i need us to start
885. 29:35talking about here is
886. 29:36kind of taking these nucleotides
887. 29:37stringing them up together
888. 29:39interacting with one another and making
889. 29:41our dna that's what we know that
890. 29:42nucleotides make up nucleic acids and
891. 29:44dna is one of them
892. 29:45before we do that we have to have a
893. 29:47quick little discussion on the concept
894. 29:49of complementarity
895. 29:50and this is honestly it's like a super
896. 29:52easy thing
897. 29:54let's say i take for example my purines
898. 29:56and i draw these out here my purines i'm
899. 29:57going to have
900. 29:58my adenine which i'm just going to
901. 29:59represent often is represented as a
902. 30:02the other one is going to be my guanine
903. 30:04often represented as
904. 30:05g the next thing you guys need to know
905. 30:08is that
906. 30:09adenine and guanine have to have an
907. 30:12interaction
908. 30:13with some of these pure pyrimidines
909. 30:16what are those interactions and that's
910. 30:18very important here
911. 30:19adenine loves to interact with thymine
912. 30:23and guanine loves to interact with
913. 30:26cytosine
914. 30:27but there's a very significant thing
915. 30:28that i want you guys to remember
916. 30:30these interactions is the basis of your
917. 30:32complementarity these are going to
918. 30:33interact with one another
919. 30:34and the way that they interact with one
920. 30:36another is actually very important
921. 30:38we're going to do it here represented in
922. 30:40blue
923. 30:41there's what's called hydrogen bonds
924. 30:44that link
925. 30:46these different nitrogenous bases
926. 30:48together between
927. 30:49guanine and cytosine and adenine and
928. 30:52thymine
929. 30:53and these hydrogen bonds that i need you
930. 30:54guys to remember is that for adenine and
931. 30:57thymine
932. 30:57there is two hydrogen bonds so what
933. 31:00should that tell you a little bit
934. 31:02that should tell you that it's probably
935. 31:03easier to break the bonds between
936. 31:05adenine and thymine than it is to break
937. 31:06the bond between
938. 31:07guanine and cytosine that comes into
939. 31:09this particular play with dna
940. 31:11replication that's why i'm telling you
941. 31:12that
942. 31:13the next thing is here we have three
943. 31:16hydrogen bonds
944. 31:17so a little bit more difficult to break
945. 31:20the bond
946. 31:21between guanine and cytosine but the bay
947. 31:23thing in egs remember that hydrogen
948. 31:24bonds
949. 31:25are weak bonds they're kind of these
950. 31:27electrostatic interactions
951. 31:29but again these are weak bonds
952. 31:32you know what's a really strong bond
953. 31:35another type of bond between the
954. 31:37phosphates and the uh the hydroxyl group
955. 31:39and that's what the one i want to talk
956. 31:41about now
957. 31:42so let's say that i take my nucleotides
958. 31:44what's a nucleotide tester knowledge
959. 31:46a phosphate group of pentose sugar in
960. 31:48that nitrogenous base i'm going to
961. 31:50string them up in a line
962. 31:52when you look at dna dna has this
963. 31:54concept of what's called a
964. 31:56anti-parallel type of arrangement so it
965. 31:58has what kind of arrangement here
966. 32:00it has an anti
967. 32:03parallel
968. 32:06arrangement and what that means is that
969. 32:08on one end
970. 32:10let's say on this left side it's a range
971. 32:13from five to three
972. 32:17and again you guys know what that means
973. 32:19we'll explain it a little bit in a
974. 32:20second
975. 32:21that means that the right aspect in this
976. 32:23case let's say this is the left
977. 32:25part of the dna the right part of the
978. 32:26dna on this right side it has to be
979. 32:29arranged in the opposite direction going
980. 32:30from top to bottom
981. 32:32which means it has to be arranged in a
982. 32:34three and
983. 32:35to five end fashion that's the concept
984. 32:38of anti-parallel dna
985. 32:40so it's moving and it's basically
986. 32:42oriented in
987. 32:43opposite directions of one another now
988. 32:46let's explain this complementarity
989. 32:48aspect with this anti-parallel strand
990. 32:51let's pretend that this pink structure
991. 32:53here this is a nitrogenous base let's
992. 32:54say that this is
993. 32:55adenine on this left strand we wanted to
994. 32:58interact with this
995. 33:00actual nitrogenous base on the right
996. 33:01strand according to complementarity
997. 33:03which one of it would have to be
998. 33:05it would have to be thymine same concept
999. 33:08here let's say that this one is
1000. 33:10which one let's say that this one is
1001. 33:12thymine
1002. 33:13which nucleotide or which nitrogenous
1003. 33:15base with this one have to be according
1004. 33:16to complementarity
1005. 33:17adenine let's use the next concept let's
1006. 33:20say that this pink one here is
1007. 33:21guanine which nucleotide do you think it
1008. 33:24would have to be
1009. 33:25according to complementarity cytosine
1010. 33:27and then let's just finish it off for
1011. 33:29the heck of it
1012. 33:29here's your cytosine which nucleotide do
1013. 33:31you think it would have to be
1014. 33:32to have interaction here according to
1015. 33:34complementarity guanine
1016. 33:36right and then for simplicity or to be
1017. 33:39you know complete
1018. 33:39how many bonds here one two three one
1019. 33:42two three
1020. 33:43one two one two hydrogen bonds
1021. 33:47the next concept here is this backbone
1022. 33:49remember i told you that there was
1023. 33:50called a sugar
1024. 33:51phosphate backbone that's the next thing
1025. 33:53i need you guys to know here's what's
1026. 33:54called a sugar
1027. 33:57phosphate backbone
1028. 34:01this sugar phosphate backbone is
1029. 34:03important because it's made up of a
1030. 34:05particular bond
1031. 34:06called a phosphodiester
1032. 34:10bond and this is a very very powerful
1033. 34:13bond
1034. 34:13a very very strong bond covalent bond if
1035. 34:17you will
1036. 34:18so i want you to remember this is a
1037. 34:19strong bond and it's
1038. 34:21formed again i told you we're going to
1039. 34:23come back to this 5
1040. 34:24and 3n thing but this strong bond is
1041. 34:27formed between
1042. 34:28the 5 end of 1 and the 3 end of another
1043. 34:32nucleotide what's on the five end you
1044. 34:34guys remember
1045. 34:35what did we say was on this five end the
1046. 34:37phosphate group we're just going to
1047. 34:38represent here's our phosphate group
1048. 34:40okay what did we say was always on the
1049. 34:42three end here we'll write it down just
1050. 34:44for simplicity sake
1051. 34:45this one is your five end this is your
1052. 34:47three and what was on the three end
1053. 34:49again
1054. 34:49the oh group i'm going to form a bond
1055. 34:52between these two structures here
1056. 34:55and when i do that that bond between the
1057. 34:58five end
1058. 34:59and the three end of one nucleotide is
1059. 35:01what makes a
1060. 35:02phosphodiester bond a very strong bond
1061. 35:05okay
1062. 35:06so now what i want to do is is i want to
1063. 35:09make a bond between each one of these
1064. 35:10a bond here phosphodiester
1065. 35:13phosphodiester phosphodiester
1066. 35:14when you do this you actually get rid of
1067. 35:16the hydrogen again we're not going to
1068. 35:17worry too much about that
1069. 35:18i just want you to know that this sugar
1070. 35:20phosphate backbone is made up of a
1071. 35:22phosphodiester bond combining phosphate
1072. 35:23of five group to the hydroxyl group of
1073. 35:25the three group
1074. 35:27of another nucleotide and so this would
1075. 35:29be our phosphodiester bond
1076. 35:31isn't that cool now that kind of gives
1077. 35:35us the basic
1078. 35:36concept here of what dna looks like
1079. 35:39sequence of nucleotides held together by
1080. 35:42phosphodiester bonds
1081. 35:44interacting anti-parallel fashion via
1082. 35:48hydrogen bonds depending upon the
1083. 35:50concept of complementarity
1084. 35:52and one strand is moving from five to
1085. 35:54three this would be your five end
1086. 35:56that would be your three end and the
1087. 35:57other one is moving in the opposite
1088. 35:59direction
1089. 36:00being a three end to five end for that
1090. 36:03anti-parallel fashion
1091. 36:05now let me take this nucleotide because
1092. 36:07this is not how
1093. 36:08um let me take this dna because this is
1094. 36:11not how dna looks like it does in a
1095. 36:12perfect world
1096. 36:13when you're drawing it out but it
1097. 36:14actually kind of has a three-dimensional
1098. 36:16shape where it starts kind of looping
1099. 36:17and looping and looping
1100. 36:18creating this double helix if you will
1101. 36:21so now here we have the dna right
1102. 36:23and the dna is in this form of a double
1103. 36:25helix and there's a couple things
1104. 36:27there's
1105. 36:27actually multiple different types of dna
1106. 36:29not a chance we're going to talk about
1107. 36:30that because it can be kind of
1108. 36:31complicated and it's not worth it
1109. 36:33so double helix is this kind of
1110. 36:35anti-parallel fashion but in a
1111. 36:36three-dimensional shape
1112. 36:38where you see the dna kind of winding
1113. 36:40around in this way
1114. 36:41when it does that it creates these
1115. 36:43little grooves if you will
1116. 36:45this groove right here is a big old
1117. 36:47groove and this groove right here that i
1118. 36:49want you to know
1119. 36:50is called the major
1120. 36:53okay it's called the major groove it's
1121. 36:55just kind of the anatomy and the
1122. 36:56topology of dna
1123. 36:58then you have another groove but this
1124. 37:01groove is a little bit tinier because of
1125. 37:03the way that the dna folds
1126. 37:05and this groove is actually the one that
1127. 37:07i really wanted to know about which is
1128. 37:08called the
1129. 37:09minor groove and the minor groove is
1130. 37:12important because guess what
1131. 37:14a lot of enzymes which are going to
1132. 37:16replicate dna
1133. 37:17or transcribe some of the dna
1134. 37:19particularly replicate the dna bind onto
1135. 37:21this portion here
1136. 37:22if i give a drug called dactinomycin
1137. 37:27ductinomycin dactynomycin kind of sits
1138. 37:30within that minor groove
1139. 37:32and what does it do it inhibits
1140. 37:35the dna from being able to replicate
1141. 37:37imagine it kind of just
1142. 37:38sitting there and an enzyme has to kind
1143. 37:41of jump into this portion to kind of go
1144. 37:42and replicate the dna
1145. 37:43it can't because it's being blocked by
1146. 37:45what thing dactynyl myosin let's pretend
1147. 37:47that the dectanomycin is this pink
1148. 37:48structure
1149. 37:49just kind of sitting in this area here
1150. 37:51and you want to bring an enzyme down to
1151. 37:53tran
1152. 37:54to replicate this dna strand but you
1153. 37:56can't because this is blocking it
1154. 37:58so that's one of the significances that
1155. 37:59i need you guys to remember with respect
1156. 38:01to the kind of topology of dna
1157. 38:03and the last little fun fact i'll give
1158. 38:05you guys is that you see this whole
1159. 38:07portion here
1160. 38:08of the dna before it makes this kind of
1161. 38:09turn to go into another little portion
1162. 38:12this right here is made up of about 10
1163. 38:14nucleotide
1164. 38:15like 10 nucleotides for each
1165. 38:19turn that you make okay so for each turn
1166. 38:2210 nucleotides then another turn
1167. 38:2410 nucleotides okay so again this
1168. 38:27really gives us a lot of detail on our
1169. 38:29dna structure
1170. 38:30a lot of the interactions let's take a
1171. 38:32quick little second to appreciate how
1172. 38:35if there's any kind of pathology or
1173. 38:37certain drugs that we can use
1174. 38:39that can alter their structure of dna or
1175. 38:42the organization of dna let's talk about
1176. 38:44that quick
1177. 38:44all right so why did i kind of talk
1178. 38:46about all this stuff and really focus on
1179. 38:47those histone proteins really
1180. 38:48significantly there was a reason why
1181. 38:50there's a clinical relevance related to
1182. 38:52it that you guys can see on your usn
1183. 38:53release
1184. 38:54particularly related to drug induced
1185. 38:55lupus so with
1186. 38:57lupus or sle right there's
1187. 39:01a it's kind of a sub type of it what
1188. 39:03happens
1189. 39:04is in these individuals their immune
1190. 39:06system
1191. 39:07right their immune system their plasma
1192. 39:09cells generate
1193. 39:10antibodies and these antibodies
1194. 39:14they target particular things you know
1195. 39:16what they target
1196. 39:17they love to target those histone
1197. 39:19proteins
1198. 39:21and whenever they target these histone
1199. 39:23proteins it leads to a lot of kind of
1200. 39:25destruction of particular cells and
1201. 39:27injury to a lot of cells
1202. 39:29and that is why it's really important so
1203. 39:32whenever somebody has drug induced lupus
1204. 39:33i guess the first question that you
1205. 39:34should have is
1206. 39:35what are the drugs that can precipitate
1207. 39:37this type of you know autoimmune or like
1208. 39:39reaction
1209. 39:40and you can remember this via the
1210. 39:42mnemonic ship
1211. 39:46and it goes sulfonamides
1212. 39:50hydralazine
1213. 39:55isoniazid which is commonly abbreviated
1214. 39:56inh
1215. 39:58procainamide which is an antiarrhythmic
1216. 40:04and then an anticonvulsant known as
1217. 40:06phenytoin
1218. 40:07these drugs can sometimes trigger an
1219. 40:10autoimmune reaction
1220. 40:11so when you're testing for drug-induced
1221. 40:13lupus it's different from when you're
1222. 40:14testing for sle even though this is kind
1223. 40:16of a type of sle
1224. 40:17in sle you test for anti-double-stranded
1225. 40:19dna anti-smith dna
1226. 40:21and drug-induced lupus you're actually
1227. 40:22testing for
1228. 40:26anti-histone
1229. 40:28antibodies okay so that is important
1230. 40:32to remember the next particular thing
1231. 40:34that i need you guys to remember is
1232. 40:35huntington's disease believe it or not
1233. 40:37huntington's disease can be related to
1234. 40:40issues with
1235. 40:41the histone proteins you know how what
1236. 40:44happens is
1237. 40:46there's issues where in histone proteins
1238. 40:48they have some issue
1239. 40:50with there's an in there's an increase
1240. 40:52in what's called
1241. 40:53a diacetylation remember what i said the
1242. 40:56d acetylation was and there was a reason
1243. 40:59why i took the time to mention that
1244. 41:01do you remember what happens when you
1245. 41:02increase d acetylation you remove acetyl
1246. 41:04groups
1247. 41:06if you remove acetyl groups from the
1248. 41:08histone proteins what did that do
1249. 41:10it tightened up the interaction between
1250. 41:12the histone and the dna if you tighten
1251. 41:13up the interaction between the histone
1252. 41:14and dna can you transcribe it
1253. 41:16no what does that result in it inhibits
1254. 41:19transcription
1255. 41:20so it's going to inhibit or decrease
1256. 41:23transcription
1257. 41:24you know why that is actually important
1258. 41:26there's a couple reasons why
1259. 41:28one is in nerves okay particularly
1260. 41:30nerves that are involved in our basal
1261. 41:32ganglia
1262. 41:33they need to release they need to
1263. 41:35transcribe particular proteins
1264. 41:37called growth factors nerve growth
1265. 41:39factors
1266. 41:40because what these nerve growth factors
1267. 41:42do is they help to stimulate nerve
1268. 41:44growth and repair and kind of some of
1269. 41:45that aspects of it right
1270. 41:47if i have some type of issue where i'm
1271. 41:49decreasing the transcription of growth
1272. 41:51factors
1273. 41:52that are helping with nerve growth
1274. 41:54what's going to happen i can lead to
1275. 41:56destruction of these nerves over time
1276. 41:57because they're not going to have the
1277. 41:58proper stimulus to continue to grow
1278. 42:00so in that situation this can lead to
1279. 42:04neuron injury
1280. 42:08and death and you know where this is
1281. 42:10particularly type of important
1282. 42:12within the basal ganglia structures with
1283. 42:15inside of the central nervous system
1284. 42:18and what happens is there is injury to
1285. 42:20particular structures
1286. 42:21within the basal ganglia and that causes
1287. 42:24a
1288. 42:24type of abnormal or hyperkinetic
1289. 42:28movement disorder
1290. 42:29and this leads to a hyper
1291. 42:32kinetic movement
1292. 42:38disorder does that make sense so again
1293. 42:41simple concept huntington's disease is
1294. 42:44related to
1295. 42:44an increase in deacetylation decreasing
1296. 42:46transcription of growth factors as well
1297. 42:48as there's a
1298. 42:49transcriptional dysregulation of the
1299. 42:51what's called the huntington's protein
1300. 42:52and abnormal proteins produced
1301. 42:54and it causes increased neuron injury
1302. 42:56and death particularly where basal
1303. 42:58ganglia
1304. 42:59and the result with hyperkinetic
1305. 43:00movements
1306. 43:02okay the last thing that i want us to
1307. 43:03talk about here
1308. 43:05is that remember that we talked a lot
1309. 43:07about purines and pyrimidines and
1310. 43:09nucleotides and all their significance
1311. 43:11because they make up dna
1312. 43:13what if i inhibited the synthesis
1313. 43:16of these purines these pyrimidines would
1314. 43:19i be able to make dna
1315. 43:21no so there's drugs that i really want
1316. 43:24you guys to remember
1317. 43:25like anti-cancer drugs wouldn't that be
1318. 43:28a perfect reason why you
1319. 43:30definitely would want to like not allow
1320. 43:31for dna to replicate as a cancer cell
1321. 43:34if i gave anti-cancer drugs or i gave
1322. 43:37drugs to
1323. 43:38individuals who have an infection and i
1324. 43:41actually inhibit the replication of
1325. 43:43bacteria
1326. 43:44i inhibit the replication of viruses i
1327. 43:45inhibit the replication of
1328. 43:47parasites so what would this be
1329. 43:50antibiotics
1330. 43:52antivirals and what else
1331. 43:56it could also be anti-parasitics
1332. 44:00and also you know what else we use these
1333. 44:02for immunosuppressants
1334. 44:05inhibiting the replication of
1335. 44:08those immune system cells that are
1336. 44:10causing a lot of havoc on our body
1337. 44:12that is important and so what we can do
1338. 44:14is we can give drugs within these
1339. 44:16categories
1340. 44:16that can inhibit purine synthesis
1341. 44:20to give you a couple i don't want to
1342. 44:22spend a ton of time on these but a lot
1343. 44:24of these are utilized
1344. 44:25for example uh some that you may want to
1345. 44:27consider here in these situations would
1346. 44:29be like what's called
1347. 44:30six mercaptopurine another one is called
1348. 44:34azathioprine
1349. 44:37another one is called ribavirin
1350. 44:42and another one is called mycophenolate
1351. 44:47six mercaptopurine and is
1352. 44:51are primarily immunosuppressant drugs
1353. 44:53ribavirin is an antiviral
1354. 44:55these would be things that would inhibit
1355. 44:57purine synthesis what if i wanted to
1356. 44:58give a drug that inhibited
1357. 45:01pyrimidine synthesis so i didn't want to
1358. 45:04make any of those pyrimidines
1359. 45:06what kind of drugs would i give here
1360. 45:08this would be things like
1361. 45:09methotrexate this would be things like
1362. 45:12what's called
1363. 45:13trimethoprim which is commonly used in
1364. 45:15what's called bacterium which is an
1365. 45:16antibiotic methotrexate is also used as
1366. 45:18immunosuppressant
1367. 45:20another one called permethamine
1368. 45:26okay so there's a bunch of this
1369. 45:27promethamine is actually an
1370. 45:28antiparasitic so you can use these
1371. 45:29different drugs to inhibit the synthesis
1372. 45:31of pyrimidines as well
1373. 45:33and the last one is what if i wanted to
1374. 45:34inhibit both of them
1375. 45:36purine and pyrimidine synthesis
1376. 45:39there's a bunch of different drugs that
1377. 45:41can do that as well one of the big ones
1378. 45:42that you guys want to remember here
1379. 45:44is hydroxy
1380. 45:48okay so that gives us the most important
1381. 45:51clinical significance related to the
1382. 45:52structure of dna
1383. 45:54all right engineers in this video today
1384. 45:55we talk about the structure of dna i
1385. 45:57hope it made sense and i hope that you
1386. 45:59guys did enjoy it alright engineers as
1387. 46:01always until next time
1388. 46:15[Music]
1389. 46:22you