WEBVTT 00:00:06.414 --> 00:00:08.748 The DNA in just one of your cells 00:00:08.748 --> 00:00:12.997 gets damaged tens of thousands of times per day. 00:00:12.997 --> 00:00:16.465 Multiply that by your body's hundred trillion or so cells, 00:00:16.465 --> 00:00:21.575 and you've got a quintillion DNA errors everyday. 00:00:21.575 --> 00:00:23.826 And because DNA provides the blueprint 00:00:23.826 --> 00:00:26.431 for the proteins your cells need to function, 00:00:26.431 --> 00:00:30.574 damage causes serious problems, such as cancer. 00:00:30.574 --> 00:00:32.634 The errors come in different forms. 00:00:32.634 --> 00:00:37.905 Sometimes nucleotides, DNA's building blocks, get damaged, 00:00:37.905 --> 00:00:41.092 other times nucleotides get matched up incorrectly, 00:00:41.092 --> 00:00:43.049 causing mutations, 00:00:43.049 --> 00:00:48.257 and nicks in one or both strands can interfere with DNA replication, 00:00:48.257 --> 00:00:52.083 or even cause sections of DNA to get mixed up. 00:00:52.083 --> 00:00:56.409 Fortunately, your cells have ways of fixing most of these problems 00:00:56.409 --> 00:00:58.119 most of the time. 00:00:58.119 --> 00:01:01.908 These repair pathways all rely on specialized enzymes. 00:01:01.908 --> 00:01:05.313 Different ones respond to different types of damage. 00:01:05.313 --> 00:01:07.882 One common error is base mismatches. 00:01:07.882 --> 00:01:10.232 Each nucleotide contains a base, 00:01:10.232 --> 00:01:12.262 and during DNA replication, 00:01:12.262 --> 00:01:16.633 the enzyme DNA polymerase is supposed to bring in the right partner 00:01:16.633 --> 00:01:20.582 to pair with every base on each template strand. 00:01:20.582 --> 00:01:24.217 Adenine with thymine, and guanine with cytosine. 00:01:24.217 --> 00:01:27.169 But about once every hundred thousand additions, 00:01:27.169 --> 00:01:28.976 it makes a mistake. 00:01:28.976 --> 00:01:31.286 The enzyme catches most of these right away, 00:01:31.286 --> 00:01:35.940 and cuts off a few nucleotides and replaces them with the correct ones. 00:01:35.940 --> 00:01:37.810 And just in case it missed a few, 00:01:37.810 --> 00:01:41.369 a second set of proteins comes behind it to check. 00:01:41.369 --> 00:01:42.848 If they find a mismatch, 00:01:42.848 --> 00:01:46.257 they cut out the incorrect nucleotide and replace it. 00:01:46.257 --> 00:01:48.478 This is called mismatch repair. 00:01:48.478 --> 00:01:52.238 Together, these two systems reduce the number of base mismatch errors 00:01:52.238 --> 00:01:55.482 to about one in one billion. 00:01:55.482 --> 00:01:59.149 But DNA can get damaged after replication, too. 00:01:59.149 --> 00:02:02.900 Lots of different molecules can cause chemical changes to nucleotides. 00:02:02.900 --> 00:02:06.245 Some of these come from environmental exposure, 00:02:06.245 --> 00:02:09.202 like certain compounds in tobacco smoke. 00:02:09.202 --> 00:02:12.349 But others are molecules that are found in cells naturally, 00:02:12.349 --> 00:02:14.917 like hydrogen peroxide. 00:02:14.917 --> 00:02:17.143 Certain chemical changes are so common 00:02:17.143 --> 00:02:21.348 that they have specific enzymes assigned to reverse the damage. 00:02:21.348 --> 00:02:24.885 But the cell also has more general repair pathways. 00:02:24.885 --> 00:02:27.231 If just one base is damaged, 00:02:27.231 --> 00:02:32.143 it can usually be fixed by a process called base excision repair. 00:02:32.143 --> 00:02:34.528 One enzyme snips out the damaged base, 00:02:34.528 --> 00:02:40.410 and other enzymes come in to trim around the site and replace the nucleotides. 00:02:40.410 --> 00:02:45.290 UV light can cause damage that's a little harder to fix. 00:02:45.290 --> 00:02:49.274 Sometimes, it causes two adjacent nucleotides to stick together, 00:02:49.274 --> 00:02:52.394 distorting the DNA's double helix shape. 00:02:52.394 --> 00:02:55.567 Damage like this requires a more complex process 00:02:55.567 --> 00:02:58.975 called nucleotide excision repair. 00:02:58.975 --> 00:03:04.015 A team of proteins removes a long strand of 24 or so nucleotides, 00:03:04.015 --> 00:03:06.745 and replaces them with fresh ones. 00:03:06.745 --> 00:03:10.700 Very high frequency radiation, like gamma rays and x-rays, 00:03:10.700 --> 00:03:13.101 cause a different kind of damage. 00:03:13.101 --> 00:03:18.285 They can actually sever one or both strands of the DNA backbone. 00:03:18.285 --> 00:03:21.303 Double strand breaks are the most dangerous. 00:03:21.303 --> 00:03:24.066 Even one can cause cell death. 00:03:24.066 --> 00:03:27.503 The two most common pathways for repairing double strand breaks 00:03:27.503 --> 00:03:33.081 are called homologous recombination and non-homologous end joining. 00:03:33.081 --> 00:03:39.186 Homologous recombination uses an undamaged section of similar DNA as a template. 00:03:39.186 --> 00:03:43.850 Enzymes interlace the damaged and undamgaed strands, 00:03:43.850 --> 00:03:46.449 get them to exchange sequences of nucleotides, 00:03:46.449 --> 00:03:49.244 and finally fill in the missing gaps 00:03:49.244 --> 00:03:53.229 to end up with two complete double-stranded segments. 00:03:53.229 --> 00:03:55.891 Non-homologous end joining, on the other hand, 00:03:55.891 --> 00:03:58.108 doesn't rely on a template. 00:03:58.108 --> 00:04:02.540 Instead, a series of proteins trims off a few nucleotides 00:04:02.540 --> 00:04:06.565 and then fuses the broken ends back together. 00:04:06.565 --> 00:04:08.554 This process isn't as accurate. 00:04:08.554 --> 00:04:12.187 It can cause genes to get mixed up, or moved around. 00:04:12.187 --> 00:04:16.332 But it's useful when sister DNA isn't available. 00:04:16.332 --> 00:04:20.149 Of course, changes to DNA aren't always bad. 00:04:20.149 --> 00:04:23.751 Beneficial mutations can allow a species to evolve. 00:04:23.751 --> 00:04:27.663 But most of the time, we want DNA to stay the same. 00:04:27.663 --> 00:04:31.776 Defects in DNA repair are associated with premature aging 00:04:31.776 --> 00:04:34.010 and many kinds of cancer. 00:04:34.010 --> 00:04:36.224 So if you're looking for a fountain of youth, 00:04:36.224 --> 00:04:39.160 it's already operating in your cells, 00:04:39.160 --> 00:04:42.719 billions and billions of times a day.