0:00:06.414,0:00:08.748 The DNA in just one of your cells 0:00:08.748,0:00:12.997 gets damaged tens of thousands [br]of times per day. 0:00:12.997,0:00:16.465 Multiply that by your body's[br]hundred trillion or so cells, 0:00:16.465,0:00:21.575 and you've got a quintillion [br]DNA errors everyday. 0:00:21.575,0:00:23.826 And because DNA provides the blueprint 0:00:23.826,0:00:26.431 for the proteins [br]your cells need to function, 0:00:26.431,0:00:30.574 damage causes serious problems,[br]such as cancer. 0:00:30.574,0:00:32.634 The errors come in different forms. 0:00:32.634,0:00:37.905 Sometimes nucleotides, [br]DNA's building blocks, get damaged, 0:00:37.905,0:00:41.092 other times nucleotides [br]get matched up incorrectly, 0:00:41.092,0:00:43.049 causing mutations, 0:00:43.049,0:00:48.257 and nicks in one or both strands[br]can interfere with DNA replication, 0:00:48.257,0:00:52.083 or even cause sections [br]of DNA to get mixed up. 0:00:52.083,0:00:56.409 Fortunately, your cells have ways[br]of fixing most of these problems 0:00:56.409,0:00:58.119 most of the time. 0:00:58.119,0:01:01.908 These repair pathways [br]all rely on specialized enzymes. 0:01:01.908,0:01:05.313 Different ones respond [br]to different types of damage. 0:01:05.313,0:01:07.882 One common error is base mismatches. 0:01:07.882,0:01:10.232 Each nucleotide contains a base, 0:01:10.232,0:01:12.262 and during DNA replication, 0:01:12.262,0:01:16.633 the enzyme DNA polymerase[br]is supposed to bring in the right partner 0:01:16.633,0:01:20.582 to pair with every base [br]on each template strand. 0:01:20.582,0:01:24.217 Adenine with thymine,[br]and guanine with cytosine. 0:01:24.217,0:01:27.169 But about once every [br]hundred thousand additions, 0:01:27.169,0:01:28.976 it makes a mistake. 0:01:28.976,0:01:31.286 The enzyme catches [br]most of these right away, 0:01:31.286,0:01:35.940 and cuts off a few nucleotides[br]and replaces them with the correct ones. 0:01:35.940,0:01:37.810 And just in case it missed a few, 0:01:37.810,0:01:41.369 a second set of proteins [br]comes behind it to check. 0:01:41.369,0:01:42.848 If they find a mismatch, 0:01:42.848,0:01:46.257 they cut out the incorrect nucleotide[br]and replace it. 0:01:46.257,0:01:48.478 This is called mismatch repair. 0:01:48.478,0:01:52.238 Together, these two systems reduce[br]the number of base mismatch errors 0:01:52.238,0:01:55.482 to about one in one billion. 0:01:55.482,0:01:59.149 But DNA can get damaged[br]after replication, too. 0:01:59.149,0:02:02.900 Lots of different molecules[br]can cause chemical changes to nucleotides. 0:02:02.900,0:02:06.245 Some of these come [br]from environmental exposure, 0:02:06.245,0:02:09.202 like certain compounds in tobacco smoke. 0:02:09.202,0:02:12.349 But others are molecules that are found[br]in cells naturally, 0:02:12.349,0:02:14.917 like hydrogen peroxide. 0:02:14.917,0:02:17.143 Certain chemical changes are so common 0:02:17.143,0:02:21.348 that they have specific enzymes assigned[br]to reverse the damage. 0:02:21.348,0:02:24.885 But the cell also has more general[br]repair pathways. 0:02:24.885,0:02:27.231 If just one base is damaged, 0:02:27.231,0:02:32.143 it can usually be fixed by a process[br]called base excision repair. 0:02:32.143,0:02:34.528 One enzyme snips out the damaged base, 0:02:34.528,0:02:40.410 and other enzymes come in to trim around[br]the site and replace the nucleotides. 0:02:40.410,0:02:45.290 UV light can cause damage [br]that's a little harder to fix. 0:02:45.290,0:02:49.274 Sometimes, it causes two adjacent[br]nucleotides to stick together, 0:02:49.274,0:02:52.394 distorting the DNA's double helix shape. 0:02:52.394,0:02:55.567 Damage like this requires [br]a more complex process 0:02:55.567,0:02:58.975 called nucleotide excision repair. 0:02:58.975,0:03:04.015 A team of proteins removes a long strand[br]of 24 or so nucleotides, 0:03:04.015,0:03:06.745 and replaces them with fresh ones. 0:03:06.745,0:03:10.700 Very high frequency radiation,[br]like gamma rays and x-rays, 0:03:10.700,0:03:13.101 cause a different kind of damage. 0:03:13.101,0:03:18.285 They can actually sever one [br]or both strands of the DNA backbone. 0:03:18.285,0:03:21.303 Double strand breaks[br]are the most dangerous. 0:03:21.303,0:03:24.066 Even one can cause cell death. 0:03:24.066,0:03:27.503 The two most common pathways[br]for repairing double strand breaks 0:03:27.503,0:03:33.081 are called homologous recombination[br]and non-homologous end joining. 0:03:33.081,0:03:39.186 Homologous recombination uses an undamaged[br]section of similar DNA as a template. 0:03:39.186,0:03:43.850 Enzymes interlace the damaged[br]and undamgaed strands, 0:03:43.850,0:03:46.449 get them to exchange sequences[br]of nucleotides, 0:03:46.449,0:03:49.244 and finally fill in the missing gaps 0:03:49.244,0:03:53.229 to end up with two complete[br]double-stranded segments. 0:03:53.229,0:03:55.891 Non-homologous end joining,[br]on the other hand, 0:03:55.891,0:03:58.108 doesn't rely on a template. 0:03:58.108,0:04:02.540 Instead, a series of proteins[br]trims off a few nucleotides 0:04:02.540,0:04:06.565 and then fuses the broken ends [br]back together. 0:04:06.565,0:04:08.554 This process isn't as accurate. 0:04:08.554,0:04:12.187 It can cause genes to get mixed up,[br]or moved around. 0:04:12.187,0:04:16.332 But it's useful when [br]sister DNA isn't available. 0:04:16.332,0:04:20.149 Of course, changes to DNA [br]aren't always bad. 0:04:20.149,0:04:23.751 Beneficial mutations [br]can allow a species to evolve. 0:04:23.751,0:04:27.663 But most of the time, [br]we want DNA to stay the same. 0:04:27.663,0:04:31.776 Defects in DNA repair are associated[br]with premature aging 0:04:31.776,0:04:34.010 and many kinds of cancer. 0:04:34.010,0:04:36.224 So if you're looking for [br]a fountain of youth, 0:04:36.224,0:04:39.160 it's already operating in your cells, 0:04:39.160,0:04:42.719 billions and billions of times a day.