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 it.

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]in 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.