1 00:00:06,414 --> 00:00:08,748 The DNA in just one of your cells 2 00:00:08,748 --> 00:00:12,997 gets damaged tens of thousands of times per day. 3 00:00:12,997 --> 00:00:16,465 Multiply that by your body's hundred trillion or so cells, 4 00:00:16,465 --> 00:00:21,575 and you've got a quintillion DNA errors everyday. 5 00:00:21,575 --> 00:00:23,826 And because DNA provides the blueprint 6 00:00:23,826 --> 00:00:26,431 for the proteins your cells need to function, 7 00:00:26,431 --> 00:00:30,574 damage causes serious problems, such as cancer. 8 00:00:30,574 --> 00:00:32,634 The errors come in different forms. 9 00:00:32,634 --> 00:00:37,905 Sometimes nucleotides, DNA's building blocks, get damaged, 10 00:00:37,905 --> 00:00:41,092 other times nucleotides get matched up incorrectly, 11 00:00:41,092 --> 00:00:43,049 causing mutations, 12 00:00:43,049 --> 00:00:48,257 and nicks in one or both strands can interfere with DNA replication, 13 00:00:48,257 --> 00:00:52,083 or even cause sections of DNA to get mixed up. 14 00:00:52,083 --> 00:00:56,409 Fortunately, your cells have ways of fixing most of these problems 15 00:00:56,409 --> 00:00:58,119 most of the time. 16 00:00:58,119 --> 00:01:01,908 These repair pathways all rely on specialized enzymes. 17 00:01:01,908 --> 00:01:05,313 Different ones respond to different types of damage. 18 00:01:05,313 --> 00:01:07,882 One common error is base mismatches. 19 00:01:07,882 --> 00:01:10,232 Each nucleotide contains a base, 20 00:01:10,232 --> 00:01:12,262 and during DNA replication, 21 00:01:12,262 --> 00:01:16,633 the enzyme DNA polymerase is supposed to bring in the right partner 22 00:01:16,633 --> 00:01:20,582 to pair with every base on each template strand. 23 00:01:20,582 --> 00:01:24,217 Adenine with thymine, and guanine with cytosine. 24 00:01:24,217 --> 00:01:27,169 But about once every hundred thousand additions, 25 00:01:27,169 --> 00:01:28,976 it makes a mistake. 26 00:01:28,976 --> 00:01:31,286 The enzyme catches most of these right away, 27 00:01:31,286 --> 00:01:35,940 and cuts off a few nucleotides and replaces them with the correct ones. 28 00:01:35,940 --> 00:01:37,810 And just in case it missed a few, 29 00:01:37,810 --> 00:01:41,369 a second set of proteins comes behind it to check it. 30 00:01:41,369 --> 00:01:42,848 If they find a mismatch, 31 00:01:42,848 --> 00:01:46,257 they cut out the incorrect nucleotide and replace it. 32 00:01:46,257 --> 00:01:48,478 This is called mismatch repair. 33 00:01:48,478 --> 00:01:52,238 Together, these two systems reduce the number of base mismatch errors 34 00:01:52,238 --> 00:01:55,482 to about one in one billion. 35 00:01:55,482 --> 00:01:59,149 But DNA can get damaged after replication, too. 36 00:01:59,149 --> 00:02:02,900 Lots of different molecules can cause chemical changes to nucleotides. 37 00:02:02,900 --> 00:02:06,245 Some of these come from environmental exposure, 38 00:02:06,245 --> 00:02:09,202 like certain compounds in tobacco smoke. 39 00:02:09,202 --> 00:02:12,349 But others are molecules that are found in cells naturally, 40 00:02:12,349 --> 00:02:14,917 like hydrogen peroxide. 41 00:02:14,917 --> 00:02:17,143 Certain chemical changes are so common 42 00:02:17,143 --> 00:02:21,348 that they have specific enzymes assigned to reverse the damage. 43 00:02:21,348 --> 00:02:24,885 But the cell also has more general repair pathways. 44 00:02:24,885 --> 00:02:27,231 If just one base is damaged, 45 00:02:27,231 --> 00:02:32,143 it can usually be fixed by a process called base excision repair. 46 00:02:32,143 --> 00:02:34,528 One enzyme snips out the damaged base, 47 00:02:34,528 --> 00:02:40,410 and other enzymes come in to trim around the site and replace the nucleotides. 48 00:02:40,410 --> 00:02:45,290 UV light can cause damage that's a little harder to fix. 49 00:02:45,290 --> 00:02:49,274 Sometimes, it causes two adjacent nucleotides to stick together, 50 00:02:49,274 --> 00:02:52,394 distorting the DNA's double helix shape. 51 00:02:52,394 --> 00:02:55,567 Damage like this requires a more complex process 52 00:02:55,567 --> 00:02:58,975 called nucleotide excision repair. 53 00:02:58,975 --> 00:03:04,015 A team of proteins removes a long strand of 24 or so nucleotides, 54 00:03:04,015 --> 00:03:06,745 and replaces them with fresh ones. 55 00:03:06,745 --> 00:03:10,700 Very high frequency radiation, like gamma rays and x-rays, 56 00:03:10,700 --> 00:03:13,101 cause a different kind of damage. 57 00:03:13,101 --> 00:03:18,285 They can actually sever one or both strands of the DNA backbone. 58 00:03:18,285 --> 00:03:21,303 Double strand breaks are the most dangerous. 59 00:03:21,303 --> 00:03:24,066 Even one can cause cell death. 60 00:03:24,066 --> 00:03:27,503 The two most common pathways for repairing double strand breaks 61 00:03:27,503 --> 00:03:33,081 are called homologous recombination and non-homologous end joining. 62 00:03:33,081 --> 00:03:39,186 Homologous recombination uses an undamaged section of similar DNA as a template. 63 00:03:39,186 --> 00:03:43,850 Enzymes interlace the damaged and undamgaed strands, 64 00:03:43,850 --> 00:03:46,449 get them to exchange sequences in nucleotides, 65 00:03:46,449 --> 00:03:49,244 and finally fill in the missing gaps 66 00:03:49,244 --> 00:03:53,229 to end up with two complete double-stranded segments. 67 00:03:53,229 --> 00:03:55,891 Non-homologous end joining, on the other hand, 68 00:03:55,891 --> 00:03:58,108 doesn't rely on a template. 69 00:03:58,108 --> 00:04:02,540 Instead, a series of proteins trims off a few nucleotides 70 00:04:02,540 --> 00:04:06,565 and then fuses the broken ends back together. 71 00:04:06,565 --> 00:04:08,554 This process isn't as accurate. 72 00:04:08,554 --> 00:04:12,187 It can cause genes to get mixed up, or moved around. 73 00:04:12,187 --> 00:04:16,332 But it's useful when sister DNA isn't available. 74 00:04:16,332 --> 00:04:20,149 Of course, changes to DNA aren't always bad. 75 00:04:20,149 --> 00:04:23,751 Beneficial mutations can allow a species to evolve. 76 00:04:23,751 --> 00:04:27,663 But most of the time, we want DNA to stay the same. 77 00:04:27,663 --> 00:04:31,776 Defects in DNA repair are associated with premature aging 78 00:04:31,776 --> 00:04:34,010 and many kinds of cancer. 79 00:04:34,010 --> 00:04:36,224 So if you're looking for a fountain of youth, 80 00:04:36,224 --> 00:04:39,160 it's already operating in your cells, 81 00:04:39,160 --> 00:04:42,719 billions and billions of times a day.