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These are the user uploaded subtitles that are being translated: 0 00:00:00,000 --> 00:00:04,110 So during meiosis, because this is a modified cell cycle, 1 00:00:04,110 --> 00:00:08,970 instead of just the G1-S-M cycle, we're going to go G1, 2 00:00:08,970 --> 00:00:10,350 we're going to replicate the DNA. 3 00:00:10,350 --> 00:00:12,388 We need all of those copies. 4 00:00:12,388 --> 00:00:14,430 But then we're going to do two meiotic divisions. 5 00:00:14,430 --> 00:00:16,620 We're going to do M1, and then we're 6 00:00:16,620 --> 00:00:18,900 going to follow this up by M2, and that 7 00:00:18,900 --> 00:00:22,080 was this two rounds of cohesin cleavage that I showed you. 8 00:00:22,080 --> 00:00:22,590 OK? 9 00:00:22,590 --> 00:00:26,647 So we're going to need to reduce the content by half, 10 00:00:26,647 --> 00:00:28,980 and the way that we're going to achieve this is not just 11 00:00:28,980 --> 00:00:33,023 one segregation but two segregations. 12 00:00:33,023 --> 00:00:37,770 13 00:00:37,770 --> 00:00:41,580 So to be able to achieve that, during M1, we're 14 00:00:41,580 --> 00:00:45,990 going to segregate the homologs from each other, so both copies 15 00:00:45,990 --> 00:00:46,830 of chromosome 1. 16 00:00:46,830 --> 00:00:50,000 17 00:00:50,000 --> 00:00:52,580 And then during M2, this is going to look a little bit more 18 00:00:52,580 --> 00:00:53,918 like a mitotic division. 19 00:00:53,918 --> 00:00:55,460 We're going to segregate the sisters. 20 00:00:55,460 --> 00:01:06,730 21 00:01:06,730 --> 00:01:08,970 So the things that we need to do are 22 00:01:08,970 --> 00:01:15,960 we need to pair the homologs, make sure 23 00:01:15,960 --> 00:01:17,430 that they can find each other. 24 00:01:17,430 --> 00:01:19,410 And there's going to be a structure, 25 00:01:19,410 --> 00:01:21,180 this really beautiful structure called 26 00:01:21,180 --> 00:01:22,770 the synaptonemal complex. 27 00:01:22,770 --> 00:01:28,210 28 00:01:28,210 --> 00:01:31,060 And it's going to assemble and basically zipper up 29 00:01:31,060 --> 00:01:32,640 along the chromosomes. 30 00:01:32,640 --> 00:01:39,690 31 00:01:39,690 --> 00:01:42,750 So number one, we're going to pair them in this way. 32 00:01:42,750 --> 00:01:46,240 Two, we're going to have this process of cutting the DNA 33 00:01:46,240 --> 00:01:48,570 and putting it back together and that process 34 00:01:48,570 --> 00:01:50,190 is called recombination. 35 00:01:50,190 --> 00:01:52,440 And we're going to do this between the homologs 36 00:01:52,440 --> 00:01:55,200 and it's going to swap genetic material around. 37 00:01:55,200 --> 00:01:58,200 We can make, in many organisms, more than one of these breaks 38 00:01:58,200 --> 00:02:00,100 and putting them back together. 39 00:02:00,100 --> 00:02:03,390 But we're going to use this to essentially also lock 40 00:02:03,390 --> 00:02:06,510 the homologs together so we get both genetic diversity 41 00:02:06,510 --> 00:02:10,289 and correct segregation all at the same time. 42 00:02:10,289 --> 00:02:12,540 We're going to use cohesin to hold these together. 43 00:02:12,540 --> 00:02:15,260 44 00:02:15,260 --> 00:02:19,220 But because of these unique cycles, 45 00:02:19,220 --> 00:02:26,690 we're going to break at the arms, cut at arms and then 46 00:02:26,690 --> 00:02:31,820 at the centromeres, then at these middle regions, 47 00:02:31,820 --> 00:02:33,410 and that cycle is going to allow us 48 00:02:33,410 --> 00:02:36,447 to achieve what we need to do. 49 00:02:36,447 --> 00:02:38,030 So I just want to draw what this looks 50 00:02:38,030 --> 00:02:39,560 like in molecular terms in case it 51 00:02:39,560 --> 00:02:41,360 wasn't as clear with my pool noodles 52 00:02:41,360 --> 00:02:43,080 as I had hoped it would be. 53 00:02:43,080 --> 00:02:45,020 And in this case, you imagine-- 54 00:02:45,020 --> 00:02:48,800 I'm going to draw two replicated sisters. 55 00:02:48,800 --> 00:02:52,650 Here is the maternal chromosome, for example. 56 00:02:52,650 --> 00:02:56,100 And then I'm going to draw the other one sort of this way. 57 00:02:56,100 --> 00:02:59,000 And so each of these is going to have cohesin surrounding it 58 00:02:59,000 --> 00:03:02,822 throughout the entire chromosome loaded during replication. 59 00:03:02,822 --> 00:03:04,280 But I'm going to do something where 60 00:03:04,280 --> 00:03:06,920 I'm going to create a break, so I'm going to come in here 61 00:03:06,920 --> 00:03:08,753 and I'm going to actually really, literally, 62 00:03:08,753 --> 00:03:09,530 cut that DNA. 63 00:03:09,530 --> 00:03:12,980 There's a DNA molecule called Spo11 that's going to cut this. 64 00:03:12,980 --> 00:03:16,290 And when I do that, I can fix it in a lot of different ways. 65 00:03:16,290 --> 00:03:21,290 So I can re-fix it, just be OK, have no crossover event. 66 00:03:21,290 --> 00:03:23,330 But I can actually recombine this 67 00:03:23,330 --> 00:03:27,350 so that this strand fixes itself with the homolog 68 00:03:27,350 --> 00:03:29,930 and this strand fixes itself there, 69 00:03:29,930 --> 00:03:31,760 and you can see that linear connectivity. 70 00:03:31,760 --> 00:03:35,670 Now we went from the father strand up to the mother strand. 71 00:03:35,670 --> 00:03:38,750 And what that's going to do is it's going to do two things. 72 00:03:38,750 --> 00:03:42,510 Now, you cannot get them apart unless you cut cohesin. 73 00:03:42,510 --> 00:03:44,900 So the only way that we could separate these, 74 00:03:44,900 --> 00:03:47,240 because we have this long strand of DNA here, 75 00:03:47,240 --> 00:03:50,340 is to eliminate those molecules up on the front. 76 00:03:50,340 --> 00:03:53,540 This is really, fundamentally, the strategy that achieves, 77 00:03:53,540 --> 00:03:56,900 again, these two things, genetic diversity 78 00:03:56,900 --> 00:03:58,710 and proper segregation. 79 00:03:58,710 --> 00:04:00,560 So physically, we need to achieve 80 00:04:00,560 --> 00:04:03,260 these events of cutting of the DNA and the recombination 81 00:04:03,260 --> 00:04:05,690 and the swapping across of the genetic material. 82 00:04:05,690 --> 00:04:08,040 There are other things that we also need to achieve. 83 00:04:08,040 --> 00:04:10,910 So for example, these two sisters 84 00:04:10,910 --> 00:04:14,390 have to go in the same direction when we segregate them, 85 00:04:14,390 --> 00:04:15,960 and so this is very different. 86 00:04:15,960 --> 00:04:19,700 So at M1, instead of them being bioriented, 87 00:04:19,700 --> 00:04:21,800 we need to co-orient the sisters. 88 00:04:21,800 --> 00:04:24,320 But otherwise, there's a lot of other similarities 89 00:04:24,320 --> 00:04:27,350 between all of the processes that we've talked about. 90 00:04:27,350 --> 00:04:31,730 Cell division is amazingly beautiful and complex. 91 00:04:31,730 --> 00:04:33,830 We have this fundamental mitotic division 92 00:04:33,830 --> 00:04:37,130 where we're going to drive these cycles again over again 93 00:04:37,130 --> 00:04:40,310 to make millions, trillions of cells in our body, 94 00:04:40,310 --> 00:04:42,470 and we have this distinct division, 95 00:04:42,470 --> 00:04:44,720 meiosis, to create the gametes, the sperm and the egg, 96 00:04:44,720 --> 00:04:45,710 for example. 97 00:04:45,710 --> 00:04:48,690 We have a very similar process of building a spindle 98 00:04:48,690 --> 00:04:51,080 and segregating, but we have this variant 99 00:04:51,080 --> 00:04:53,720 where we have two meiotic divisions instead with the need 100 00:04:53,720 --> 00:04:55,218 to start with this recombination. 101 00:04:55,218 --> 00:04:57,260 So in the next lecture, we're going to come back. 102 00:04:57,260 --> 00:04:59,420 We're going to discuss these events again. 103 00:04:59,420 --> 00:05:01,837 But instead of just thinking about these physical events-- 104 00:05:01,837 --> 00:05:03,857 how do you pair DNA, how do you segregate it, 105 00:05:03,857 --> 00:05:04,940 how do you distribute it-- 106 00:05:04,940 --> 00:05:07,273 we're going to talk about that regulatory component, how 107 00:05:07,273 --> 00:05:07,880 we time that. 108 00:05:07,880 --> 00:05:10,255 How do we know that we're doing things correctly 109 00:05:10,255 --> 00:05:11,630 and that we're not moving forward 110 00:05:11,630 --> 00:05:13,320 in the presence of errors? 111 00:05:13,320 --> 00:05:15,850 So I'll see you all for the next lecture. 8464

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