[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:06.41,0:00:08.75,Default,,0000,0000,0000,,The DNA in just one of your cells
Dialogue: 0,0:00:08.75,0:00:12.100,Default,,0000,0000,0000,,gets damaged tens of thousands \Nof times per day.
Dialogue: 0,0:00:12.100,0:00:16.46,Default,,0000,0000,0000,,Multiply that by your body's\Nhundred trillion or so cells,
Dialogue: 0,0:00:16.46,0:00:21.58,Default,,0000,0000,0000,,and you've got a quintillion \NDNA errors everyday.
Dialogue: 0,0:00:21.58,0:00:23.83,Default,,0000,0000,0000,,And because DNA provides the blueprint
Dialogue: 0,0:00:23.83,0:00:26.43,Default,,0000,0000,0000,,for the proteins \Nyour cells need to function,
Dialogue: 0,0:00:26.43,0:00:30.57,Default,,0000,0000,0000,,damage causes serious problems,\Nsuch as cancer.
Dialogue: 0,0:00:30.57,0:00:32.63,Default,,0000,0000,0000,,The errors come in different forms.
Dialogue: 0,0:00:32.63,0:00:37.90,Default,,0000,0000,0000,,Sometimes nucleotides, \NDNA's building blocks, get damaged,
Dialogue: 0,0:00:37.90,0:00:41.09,Default,,0000,0000,0000,,other times nucleotides \Nget matched up incorrectly,
Dialogue: 0,0:00:41.09,0:00:43.05,Default,,0000,0000,0000,,causing mutations,
Dialogue: 0,0:00:43.05,0:00:48.26,Default,,0000,0000,0000,,and nicks in one or both strands\Ncan interfere with DNA replication,
Dialogue: 0,0:00:48.26,0:00:52.08,Default,,0000,0000,0000,,or even cause sections \Nof DNA to get mixed up.
Dialogue: 0,0:00:52.08,0:00:56.41,Default,,0000,0000,0000,,Fortunately, your cells have ways\Nof fixing most of these problems
Dialogue: 0,0:00:56.41,0:00:58.12,Default,,0000,0000,0000,,most of the time.
Dialogue: 0,0:00:58.12,0:01:01.91,Default,,0000,0000,0000,,These repair pathways \Nall rely on specialized enzymes.
Dialogue: 0,0:01:01.91,0:01:05.31,Default,,0000,0000,0000,,Different ones respond \Nto different types of damage.
Dialogue: 0,0:01:05.31,0:01:07.88,Default,,0000,0000,0000,,One common error is base mismatches.
Dialogue: 0,0:01:07.88,0:01:10.23,Default,,0000,0000,0000,,Each nucleotide contains a base,
Dialogue: 0,0:01:10.23,0:01:12.26,Default,,0000,0000,0000,,and during DNA replication,
Dialogue: 0,0:01:12.26,0:01:16.63,Default,,0000,0000,0000,,the enzyme DNA polymerase\Nis supposed to bring in the right partner
Dialogue: 0,0:01:16.63,0:01:20.58,Default,,0000,0000,0000,,to pair with every base \Non each template strand.
Dialogue: 0,0:01:20.58,0:01:24.22,Default,,0000,0000,0000,,Adenine with thymine,\Nand guanine with cytosine.
Dialogue: 0,0:01:24.22,0:01:27.17,Default,,0000,0000,0000,,But about once every \Nhundred thousand additions,
Dialogue: 0,0:01:27.17,0:01:28.98,Default,,0000,0000,0000,,it makes a mistake.
Dialogue: 0,0:01:28.98,0:01:31.29,Default,,0000,0000,0000,,The enzyme catches \Nmost of these right away,
Dialogue: 0,0:01:31.29,0:01:35.94,Default,,0000,0000,0000,,and cuts off a few nucleotides\Nand replaces them with the correct ones.
Dialogue: 0,0:01:35.94,0:01:37.81,Default,,0000,0000,0000,,And just in case it missed a few,
Dialogue: 0,0:01:37.81,0:01:41.37,Default,,0000,0000,0000,,a second set of proteins \Ncomes behind it to check.
Dialogue: 0,0:01:41.37,0:01:42.85,Default,,0000,0000,0000,,If they find a mismatch,
Dialogue: 0,0:01:42.85,0:01:46.26,Default,,0000,0000,0000,,they cut out the incorrect nucleotide\Nand replace it.
Dialogue: 0,0:01:46.26,0:01:48.48,Default,,0000,0000,0000,,This is called mismatch repair.
Dialogue: 0,0:01:48.48,0:01:52.24,Default,,0000,0000,0000,,Together, these two systems reduce\Nthe number of base mismatch errors
Dialogue: 0,0:01:52.24,0:01:55.48,Default,,0000,0000,0000,,to about one in one billion.
Dialogue: 0,0:01:55.48,0:01:59.15,Default,,0000,0000,0000,,But DNA can get damaged\Nafter replication, too.
Dialogue: 0,0:01:59.15,0:02:02.90,Default,,0000,0000,0000,,Lots of different molecules\Ncan cause chemical changes to nucleotides.
Dialogue: 0,0:02:02.90,0:02:06.24,Default,,0000,0000,0000,,Some of these come \Nfrom environmental exposure,
Dialogue: 0,0:02:06.24,0:02:09.20,Default,,0000,0000,0000,,like certain compounds in tobacco smoke.
Dialogue: 0,0:02:09.20,0:02:12.35,Default,,0000,0000,0000,,But others are molecules that are found\Nin cells naturally,
Dialogue: 0,0:02:12.35,0:02:14.92,Default,,0000,0000,0000,,like hydrogen peroxide.
Dialogue: 0,0:02:14.92,0:02:17.14,Default,,0000,0000,0000,,Certain chemical changes are so common
Dialogue: 0,0:02:17.14,0:02:21.35,Default,,0000,0000,0000,,that they have specific enzymes assigned\Nto reverse the damage.
Dialogue: 0,0:02:21.35,0:02:24.88,Default,,0000,0000,0000,,But the cell also has more general\Nrepair pathways.
Dialogue: 0,0:02:24.88,0:02:27.23,Default,,0000,0000,0000,,If just one base is damaged,
Dialogue: 0,0:02:27.23,0:02:32.14,Default,,0000,0000,0000,,it can usually be fixed by a process\Ncalled base excision repair.
Dialogue: 0,0:02:32.14,0:02:34.53,Default,,0000,0000,0000,,One enzyme snips out the damaged base,
Dialogue: 0,0:02:34.53,0:02:40.41,Default,,0000,0000,0000,,and other enzymes come in to trim around\Nthe site and replace the nucleotides.
Dialogue: 0,0:02:40.41,0:02:45.29,Default,,0000,0000,0000,,UV light can cause damage \Nthat's a little harder to fix.
Dialogue: 0,0:02:45.29,0:02:49.27,Default,,0000,0000,0000,,Sometimes, it causes two adjacent\Nnucleotides to stick together,
Dialogue: 0,0:02:49.27,0:02:52.39,Default,,0000,0000,0000,,distorting the DNA's double helix shape.
Dialogue: 0,0:02:52.39,0:02:55.57,Default,,0000,0000,0000,,Damage like this requires \Na more complex process
Dialogue: 0,0:02:55.57,0:02:58.98,Default,,0000,0000,0000,,called nucleotide excision repair.
Dialogue: 0,0:02:58.98,0:03:04.02,Default,,0000,0000,0000,,A team of proteins removes a long strand\Nof 24 or so nucleotides,
Dialogue: 0,0:03:04.02,0:03:06.74,Default,,0000,0000,0000,,and replaces them with fresh ones.
Dialogue: 0,0:03:06.74,0:03:10.70,Default,,0000,0000,0000,,Very high frequency radiation,\Nlike gamma rays and x-rays,
Dialogue: 0,0:03:10.70,0:03:13.10,Default,,0000,0000,0000,,cause a different kind of damage.
Dialogue: 0,0:03:13.10,0:03:18.28,Default,,0000,0000,0000,,They can actually sever one \Nor both strands of the DNA backbone.
Dialogue: 0,0:03:18.28,0:03:21.30,Default,,0000,0000,0000,,Double strand breaks\Nare the most dangerous.
Dialogue: 0,0:03:21.30,0:03:24.07,Default,,0000,0000,0000,,Even one can cause cell death.
Dialogue: 0,0:03:24.07,0:03:27.50,Default,,0000,0000,0000,,The two most common pathways\Nfor repairing double strand breaks
Dialogue: 0,0:03:27.50,0:03:33.08,Default,,0000,0000,0000,,are called homologous recombination\Nand non-homologous end joining.
Dialogue: 0,0:03:33.08,0:03:39.19,Default,,0000,0000,0000,,Homologous recombination uses an undamaged\Nsection of similar DNA as a template.
Dialogue: 0,0:03:39.19,0:03:43.85,Default,,0000,0000,0000,,Enzymes interlace the damaged\Nand undamgaed strands,
Dialogue: 0,0:03:43.85,0:03:46.45,Default,,0000,0000,0000,,get them to exchange sequences\Nof nucleotides,
Dialogue: 0,0:03:46.45,0:03:49.24,Default,,0000,0000,0000,,and finally fill in the missing gaps
Dialogue: 0,0:03:49.24,0:03:53.23,Default,,0000,0000,0000,,to end up with two complete\Ndouble-stranded segments.
Dialogue: 0,0:03:53.23,0:03:55.89,Default,,0000,0000,0000,,Non-homologous end joining,\Non the other hand,
Dialogue: 0,0:03:55.89,0:03:58.11,Default,,0000,0000,0000,,doesn't rely on a template.
Dialogue: 0,0:03:58.11,0:04:02.54,Default,,0000,0000,0000,,Instead, a series of proteins\Ntrims off a few nucleotides
Dialogue: 0,0:04:02.54,0:04:06.56,Default,,0000,0000,0000,,and then fuses the broken ends \Nback together.
Dialogue: 0,0:04:06.56,0:04:08.55,Default,,0000,0000,0000,,This process isn't as accurate.
Dialogue: 0,0:04:08.55,0:04:12.19,Default,,0000,0000,0000,,It can cause genes to get mixed up,\Nor moved around.
Dialogue: 0,0:04:12.19,0:04:16.33,Default,,0000,0000,0000,,But it's useful when \Nsister DNA isn't available.
Dialogue: 0,0:04:16.33,0:04:20.15,Default,,0000,0000,0000,,Of course, changes to DNA \Naren't always bad.
Dialogue: 0,0:04:20.15,0:04:23.75,Default,,0000,0000,0000,,Beneficial mutations \Ncan allow a species to evolve.
Dialogue: 0,0:04:23.75,0:04:27.66,Default,,0000,0000,0000,,But most of the time, \Nwe want DNA to stay the same.
Dialogue: 0,0:04:27.66,0:04:31.78,Default,,0000,0000,0000,,Defects in DNA repair are associated\Nwith premature aging
Dialogue: 0,0:04:31.78,0:04:34.01,Default,,0000,0000,0000,,and many kinds of cancer.
Dialogue: 0,0:04:34.01,0:04:36.22,Default,,0000,0000,0000,,So if you're looking for \Na fountain of youth,
Dialogue: 0,0:04:36.22,0:04:39.16,Default,,0000,0000,0000,,it's already operating in your cells,
Dialogue: 0,0:04:39.16,0:04:42.72,Default,,0000,0000,0000,,billions and billions of times a day.