Lesson 5 – Video 2b
2014 [00:00:01.92] PROFESSOR: Hi. In this video, we'll talk about three different ways that
2015 repairs damaged DNA. In method one, we'll talk about base excision repair. This is
2016 single base is affected. In this case, there's a type of damage called deamination.
2017 [00:00:19.30] This is when a C base within an amino group is deaminated. And then
you have a
2018 base which has a carbonyl group in place of the nitrogen. And coincidentally, this base
2019 the base that is in RNA.
2020 [00:00:38.77] Now, you'll remember that uracil acts the same, base pairs the same as
a T. And so
2021 this seems to the DNA like a C to T mutation. But they're also special enzymes-- for
2022 DNA glycosylase-- that recognizes that uracil is not to be incorporated into to DNA. It's
[00:01:07.32] And so it'll scan the genome for places where a 2024 U is present. When it
finds it, it
2025 will excise the base, then cut the backbones of the sugar and phosphate groups, insert
2026 base, which is done by DNA polymerase. And then DNA ligase will seal the nick.
2027 [00:01:34.01] There is another type of DNA damage called depurination, which
2028 purines, which are G's or C's. And those effect the bond between the sugar and the
base. And the
2029 bases will be lost. And so those types of mutations or DNA errors enter this flow chart
2031 [00:02:00.30] So these are both two very common kinds of mutations. And they are
repaired 2032 effectively by the cell. However not perfectly, we can actually see evolutionarily that
2033 more C to T mutations then other types of base pair changes. So again, it's very
2034 occurring event. And the cell catches most of them.
2035 [00:02:27.67] A second type of method is called nucleotide excision repair. In this case,
2036 more bases can be affected. And the type of damage shown here is a pyrimidine
dimer, which is
2037 a more generic term for the type of damage we saw in the previous video, thymine
2038 thymidine dimers. So this is a pyrimidine dimer. Instead of TT, we have a CT base pair.
2039 [00:02:56.82] And once, again there are proteins which constantly scan and surveil the
2040 When it finds this kind of an error, it will cleave the backbone at some distance from the
2041 site, remove the entire piece of DNA using the enzyme DNA helicase. DNA polymerase
2042 in the temple plate 3 ' to 5 ', and ligase will seal the final nick. So again, this is an
2043 mechanism for repairing thymidine dimers.
2044 [00:03:37.51] So now we're going to ask, before we get to the third mechanism, we're
2045 ask the question, how does the cell know when it encounters a bubble or a mutation?
How does it
2046 know which strand to repair? This picture is not very realistic, because really the
bubble is on
2047 both sides. It implies that the correct base is a straight and normal backbone. And then
2048 you have an incredible base, it bubbles out a little bit.
2049 [00:04:09.87] But obviously that's not the case. After replication, a T will be inserted
next to the
2050 A. And a C will properly be inserted next to the G. And going on, you would have 50%
mutated 2051 cells and 50% non-mutated cells. Now let's-- although we don't know how yet-- if the
2052 somehow that the A is the incorrect base, it can correct that. And then it can put 2 G's
2053 now you'll have 100% correct, of the cells progeny will have the correct genome.
2054 [00:05:00.68] But think about the consequences if the incorrect base is repaired, if the
G is cut
2055 out and it gets converted to a T. Now you have 100% of the progeny cells having the
2056 incorporated. So how does the cell figure out which is the proper base to go at that
2057 [00:05:25.76] The answer is quite ingenious. And what the cell does-- which gets it
right most of
2058 the time, but not every time-- is it will, once it finds a mismatch, here, it will scan in both
2059 directions, looking for the closest to nick in the backbone of the strand. The cell then
2060 that this is the most recently synthesized strand, the other strand with no nicks having
2061 test of time, per se.
[00:06:01.63] And so it will decide to cut out the region of the 2062 DNA that has the pre-
2063 nick. And it will repair that-- again, with I should draw it like that-- with a polymerase,
2064 ligase sealing the final nick. As you might guess, this all happens relatively quickly,
2065 DNA synthesis.
2066 [00:06:29.73] Because if a different enzyme happens to notice there's a nick present in
2067 it will repair that not knowing that there's a bulge there. So after synthesis, the DNA is
2068 a ticking time bomb, where the cell has to repair this bulge before another enzyme
2069 nick, if it's going to use this mechanism for picking out which