1 00:00:00,930 --> 00:00:02,130 [Instructor] Hello, and welcome 2 00:00:02,130 --> 00:00:05,220 to the second lecture in module three. 3 00:00:05,220 --> 00:00:08,430 This lecture is going to be on DNA replication, 4 00:00:08,430 --> 00:00:10,140 and this lecture is going to be a bit shorter, 5 00:00:10,140 --> 00:00:12,510 and it's really just to help prepare you 6 00:00:12,510 --> 00:00:15,630 to understand mitosis and meiosis. 7 00:00:15,630 --> 00:00:17,790 But given that this is a bit of a different topic, 8 00:00:17,790 --> 00:00:19,893 I wanted to cover it separately. 9 00:00:20,790 --> 00:00:23,520 So how do new cells get their DNA? 10 00:00:23,520 --> 00:00:26,190 And so, as we've talked about before, 11 00:00:26,190 --> 00:00:29,550 you get your complete genome from the moment of conception 12 00:00:29,550 --> 00:00:33,030 when the sperm fuses with the egg 13 00:00:33,030 --> 00:00:38,030 and you have your full compliments of 46 chromosomes total, 14 00:00:38,880 --> 00:00:40,323 23 pairs, 15 00:00:41,773 --> 00:00:43,377 one of each that came from your mother 16 00:00:43,377 --> 00:00:45,360 and one of each that came from your father. 17 00:00:45,360 --> 00:00:46,740 The chromosomes that come from your mother 18 00:00:46,740 --> 00:00:49,230 are called your maternal chromosomes. 19 00:00:49,230 --> 00:00:50,700 And the chromosomes that come from your father 20 00:00:50,700 --> 00:00:52,020 are called paternal chromosomes. 21 00:00:52,020 --> 00:00:54,630 We start out as one of these single fertilized eggs. 22 00:00:54,630 --> 00:00:56,880 That single egg is a single cell. 23 00:00:56,880 --> 00:00:58,890 It will divide many times during development 24 00:00:58,890 --> 00:01:01,020 to form a fully developed human 25 00:01:01,020 --> 00:01:03,360 made of trillions of cells. 26 00:01:03,360 --> 00:01:06,270 As a result, the complete genomes, all 46 chromosomes, 27 00:01:06,270 --> 00:01:08,970 is replicated prior to each cell division 28 00:01:08,970 --> 00:01:11,640 using each of the two strands of DNA as a template 29 00:01:11,640 --> 00:01:13,620 for a new complementary strand. 30 00:01:13,620 --> 00:01:16,110 And we'll take a look at what that actually looks like 31 00:01:16,110 --> 00:01:17,310 in the next slide. 32 00:01:17,310 --> 00:01:20,760 But basically, it's a way to create an identical copy 33 00:01:20,760 --> 00:01:22,620 of each chromosome. 34 00:01:22,620 --> 00:01:24,600 It is critical that each of these replications 35 00:01:24,600 --> 00:01:26,370 are highly accurate, 36 00:01:26,370 --> 00:01:29,040 as all 6 billion bases are in the right order 37 00:01:29,040 --> 00:01:30,300 every single time. 38 00:01:30,300 --> 00:01:31,350 That's a tall order, 39 00:01:31,350 --> 00:01:35,580 and the cell actually does a phenomenally good job of this. 40 00:01:35,580 --> 00:01:38,280 And I'll give you some statistics on that in a moment. 41 00:01:39,210 --> 00:01:41,730 So what is the mechanism of replication? 42 00:01:41,730 --> 00:01:45,660 Again, remember we start with double stranded DNA, 43 00:01:45,660 --> 00:01:48,333 and what happens is, is you can see here, 44 00:01:50,040 --> 00:01:52,410 the double stranded DNA, which is base paired 45 00:01:52,410 --> 00:01:55,410 between the two complimentary strands 46 00:01:55,410 --> 00:01:58,170 actually starts to unzip or unwind. 47 00:01:58,170 --> 00:02:01,620 And as that occurs, we start to have formation 48 00:02:01,620 --> 00:02:04,020 of a new complimentary strand 49 00:02:04,020 --> 00:02:06,573 to each one of those original strands. 50 00:02:09,540 --> 00:02:11,640 And these new complimentary strands, or also, 51 00:02:11,640 --> 00:02:14,640 will base pair with each of those other strands. 52 00:02:14,640 --> 00:02:16,860 So as a result, in the end, 53 00:02:16,860 --> 00:02:20,703 you have two identical double stranded copies of DNA. 54 00:02:22,260 --> 00:02:24,420 Now it's important, as I mentioned, it's important 55 00:02:24,420 --> 00:02:28,050 to do this in as error-free a way as possible. 56 00:02:28,050 --> 00:02:32,130 And when we talk about the error rate, 57 00:02:32,130 --> 00:02:34,980 we're talking about really the fidelity of, 58 00:02:34,980 --> 00:02:38,880 you know, how well the copies are being duplicated 59 00:02:38,880 --> 00:02:41,130 and creating identical copies 60 00:02:41,130 --> 00:02:44,430 with each round of replication. 61 00:02:44,430 --> 00:02:46,140 But errors do happen. 62 00:02:46,140 --> 00:02:49,710 About one in 10,000 base pairs has a mismatch occur, 63 00:02:49,710 --> 00:02:51,540 a G or a C with an A or a T, 64 00:02:51,540 --> 00:02:53,310 as opposed to just A and T together 65 00:02:53,310 --> 00:02:54,663 or G and C together. 66 00:02:55,590 --> 00:02:57,690 But the cells come up with a very clever way 67 00:02:57,690 --> 00:02:58,680 of dealing with this. 68 00:02:58,680 --> 00:03:00,843 It has mechanisms called proofreading, 69 00:03:01,680 --> 00:03:05,340 where a protein called DNA polymerase, 70 00:03:05,340 --> 00:03:07,590 will actually review the newly formed strand 71 00:03:07,590 --> 00:03:08,820 for these mismatches 72 00:03:08,820 --> 00:03:12,630 or the places where G is binding to a T or an A 73 00:03:12,630 --> 00:03:15,390 or where C is binding to a T or an A. 74 00:03:15,390 --> 00:03:16,800 And the DNA polymerase, 75 00:03:16,800 --> 00:03:18,690 when it finds one of these mismatches, 76 00:03:18,690 --> 00:03:20,610 will actually replace one of the two bases 77 00:03:20,610 --> 00:03:23,100 with its matching base. 78 00:03:23,100 --> 00:03:26,070 With proofreading, DNA replication errors occur only 79 00:03:26,070 --> 00:03:29,760 in one in every one billion, billion with a B, bases. 80 00:03:29,760 --> 00:03:32,220 And the entire six billion bases are replicated 81 00:03:32,220 --> 00:03:33,660 in a matter of hours. 82 00:03:33,660 --> 00:03:37,650 So can you try to imagine replicating six billion bases 83 00:03:37,650 --> 00:03:40,890 in six hours and only getting two wrong? (chuckles) 84 00:03:40,890 --> 00:03:42,630 Our cells are really, really good. 85 00:03:42,630 --> 00:03:47,630 I mean that is a phenomenal rate of fidelity 86 00:03:47,820 --> 00:03:51,330 and rate of speed for this whole process to occur. 87 00:03:51,330 --> 00:03:53,790 And it happens, it happens many, many times 88 00:03:53,790 --> 00:03:57,030 as the person develops, as cells are needed to divide. 89 00:03:57,030 --> 00:03:58,950 Each and every time a cell divides, 90 00:03:58,950 --> 00:04:01,260 you need to have the DNA replicated 91 00:04:01,260 --> 00:04:03,120 so that the two new cells that form 92 00:04:03,120 --> 00:04:06,810 from this one original cell each can have a full copy 93 00:04:06,810 --> 00:04:07,643 of the genome. 94 00:04:10,260 --> 00:04:12,120 So let's take a quick peek at proofreading. 95 00:04:12,120 --> 00:04:16,980 So as I mentioned, it's basically when you have in place, 96 00:04:16,980 --> 00:04:20,730 in this case, it's looking at a G is being paired with a T. 97 00:04:20,730 --> 00:04:22,080 So this should have been, right, 98 00:04:22,080 --> 00:04:24,840 what base should this have been instead of a G? 99 00:04:24,840 --> 00:04:26,910 It should have been an A. How do we know that? 100 00:04:26,910 --> 00:04:28,140 Well, we know that because, 101 00:04:28,140 --> 00:04:30,450 on the complementary strand, there is a T. 102 00:04:30,450 --> 00:04:32,550 So we know in order for its base pair properly, 103 00:04:32,550 --> 00:04:34,173 it would have to be an A. 104 00:04:35,100 --> 00:04:38,760 The DNA polymerase will recognize this mismatch 105 00:04:38,760 --> 00:04:41,460 and remove the mismatching base. 106 00:04:41,460 --> 00:04:42,870 So it'll remove the G in this case, 107 00:04:42,870 --> 00:04:45,720 and it will replace it with the proper base of an A. 108 00:04:45,720 --> 00:04:50,720 So the DNA polymerase actually scans the entire 109 00:04:50,790 --> 00:04:52,920 newly formed strands of DNA 110 00:04:52,920 --> 00:04:57,270 and will replace and repair as many of these as it can. 111 00:04:57,270 --> 00:05:00,600 Instead of having an error one in 10,000 bases, 112 00:05:00,600 --> 00:05:04,080 the error rate declines to one in one billion bases, 113 00:05:04,080 --> 00:05:05,820 which is a huge improvement. 114 00:05:05,820 --> 00:05:10,820 So having proper DNA replication proofreading apparatus 115 00:05:11,160 --> 00:05:12,660 in place is really important 116 00:05:12,660 --> 00:05:16,740 for maintaining the fidelity of the the DNA 117 00:05:16,740 --> 00:05:18,420 with every cell division. 118 00:05:18,420 --> 00:05:20,880 So let's take a quick peek at what this actually looks like. 119 00:05:20,880 --> 00:05:23,250 So on the left here, what we're looking at 120 00:05:23,250 --> 00:05:26,460 is the original double stranded DNA molecule, 121 00:05:26,460 --> 00:05:27,840 looking at it like, again, 122 00:05:27,840 --> 00:05:31,110 the two complimentary strands base paired together, 123 00:05:31,110 --> 00:05:32,760 sort of like the rungs on the ladder. 124 00:05:32,760 --> 00:05:34,920 It starts to unzip, and as it does, 125 00:05:34,920 --> 00:05:36,730 new strands begin forming 126 00:05:37,950 --> 00:05:40,320 on each of the two complimentary strands. 127 00:05:40,320 --> 00:05:43,080 And in the end, you have two identical strands 128 00:05:43,080 --> 00:05:44,340 to one another, 129 00:05:44,340 --> 00:05:47,370 two identical double stranded DNA molecules. 130 00:05:47,370 --> 00:05:51,123 And each of these has a new complementary strand to it. 131 00:05:52,020 --> 00:05:53,760 So now when the cell divides, 132 00:05:53,760 --> 00:05:57,780 one of the cells can get one of these copies 133 00:05:57,780 --> 00:05:59,340 and the other cell can get the other copy. 134 00:05:59,340 --> 00:06:00,930 And in the end, you have two cells 135 00:06:00,930 --> 00:06:03,933 that have identical DNA to the original cell. 136 00:06:05,250 --> 00:06:07,380 What does this actually look like in a karyotype? 137 00:06:07,380 --> 00:06:10,260 Just want to show you here. 138 00:06:10,260 --> 00:06:11,790 So, because it can get kind of confusing, 139 00:06:11,790 --> 00:06:14,070 because here we're talking about duplicating chromosomes, 140 00:06:14,070 --> 00:06:16,740 as opposed to homologous chromosomes. 141 00:06:16,740 --> 00:06:18,150 What were homologous chromosomes? 142 00:06:18,150 --> 00:06:19,710 Those were the copies of chromosomes 143 00:06:19,710 --> 00:06:21,060 where you received one from the mother 144 00:06:21,060 --> 00:06:22,830 and one from your father. 145 00:06:22,830 --> 00:06:25,140 What we're talking about here is actually 146 00:06:25,140 --> 00:06:27,840 creating an identical copy of each one of those. 147 00:06:27,840 --> 00:06:30,453 So for Chromosome 1, for example, 148 00:06:32,100 --> 00:06:34,170 after DNA replication has occurred, 149 00:06:34,170 --> 00:06:37,013 you can see there are two copies 150 00:06:39,660 --> 00:06:41,640 of each one of these two chromosomes. 151 00:06:41,640 --> 00:06:46,440 So what we would say is these two chromosomes 152 00:06:46,440 --> 00:06:48,360 are homologous to one another 153 00:06:48,360 --> 00:06:51,060 because one came originally from the individual's mother, 154 00:06:51,060 --> 00:06:53,220 one came from the individual's father. 155 00:06:53,220 --> 00:06:54,870 And then we would also, to look, 156 00:06:54,870 --> 00:06:57,660 we would also look at the duplicated chromosomes 157 00:06:57,660 --> 00:07:00,030 and what these are called, sister chromatids. 158 00:07:00,030 --> 00:07:01,530 Sister chromatids. 159 00:07:01,530 --> 00:07:03,570 That just means identical copies 160 00:07:03,570 --> 00:07:05,160 of the same chromosome. 161 00:07:05,160 --> 00:07:06,180 Not homologous. 162 00:07:06,180 --> 00:07:08,670 Remember homologous, there are slight differences. 163 00:07:08,670 --> 00:07:11,370 While they're both still Chromosome 1, 164 00:07:11,370 --> 00:07:12,970 they have slight differences 165 00:07:14,134 --> 00:07:15,510 because you received one from your mother 166 00:07:15,510 --> 00:07:16,343 and one from your father, 167 00:07:16,343 --> 00:07:17,760 and those are going to be a little bit different 168 00:07:17,760 --> 00:07:19,290 from one another. 169 00:07:19,290 --> 00:07:20,970 Sister chromatids, on the other hand, 170 00:07:20,970 --> 00:07:22,860 are identical copies to one another. 171 00:07:22,860 --> 00:07:25,890 So the only differences between sister chromatids, 172 00:07:25,890 --> 00:07:30,180 so the only differences between, say, this DNA molecule 173 00:07:30,180 --> 00:07:34,080 and this DNA molecule would be any of those very, 174 00:07:34,080 --> 00:07:38,940 very rare errors that occurred during replication. 175 00:07:38,940 --> 00:07:43,940 So, unlikely to even be a single error that's occurred 176 00:07:44,280 --> 00:07:45,483 in this one chromosome. 177 00:07:47,940 --> 00:07:50,340 Let's pull this all together for a quick summary. 178 00:07:50,340 --> 00:07:53,190 So prior to cell division, the genome is replicated 179 00:07:53,190 --> 00:07:55,500 to have one genome for each of the two cells 180 00:07:55,500 --> 00:07:57,720 that will result from cell division. 181 00:07:57,720 --> 00:08:00,450 Each strand of double stranded DNA molecules serves 182 00:08:00,450 --> 00:08:03,810 as a template for a new complementary strand to form. 183 00:08:03,810 --> 00:08:05,700 Errors in replication are rare 184 00:08:05,700 --> 00:08:07,620 and are generally repaired with proofreading 185 00:08:07,620 --> 00:08:08,760 for base mismatches. 186 00:08:08,760 --> 00:08:12,420 However, a few errors do occur with each replication. 187 00:08:12,420 --> 00:08:13,306 The end result of DNA replication 188 00:08:13,306 --> 00:08:15,900 is identical sister chromatids 189 00:08:15,900 --> 00:08:18,930 making up each of the 46 chromosomes. 190 00:08:18,930 --> 00:08:21,330 So each of those 46 chromosomes has been duplicated, 191 00:08:21,330 --> 00:08:23,670 so they each have a sister chromatid. 192 00:08:23,670 --> 00:08:26,400 And during the process, which we will talk about next 193 00:08:26,400 --> 00:08:30,630 in the process of mitosis, where cells will divide, 194 00:08:30,630 --> 00:08:33,840 each of these cells that forms from the process of division 195 00:08:33,840 --> 00:08:36,540 will receive one of those sister chromatids. 196 00:08:36,540 --> 00:08:37,800 So what's next in this module? 197 00:08:37,800 --> 00:08:39,840 Well, I kind of just gave it away a little bit. (chuckles) 198 00:08:39,840 --> 00:08:41,100 What we're going to be talking about next 199 00:08:41,100 --> 00:08:42,750 is mitosis and meiosis 200 00:08:42,750 --> 00:08:46,800 and start to better understand the process of cell division. 201 00:08:46,800 --> 00:08:48,510 So with that, I will say goodbye 202 00:08:48,510 --> 00:08:50,810 and I will speak with you in the next lecture.