Lesson 5 – Video 1b
1799 [00:00:01.53] PROFESSOR: We'll continue our discussion of DNAreplication with
1800 about the replication of the telomere sequences-- that is, replication at the ends of the
1801 chromosomes. Now here, you see a schematic of a chromosome, a piece of double
1802 DNAwith three origins of replication. You have three replication bubbles forming.
1803 [00:00:24.06] When these bubbles collide, that's fine. That means you've completed that
1804 And since you have the leading strand here, there'll be no problem synthesizing this
1805 prime to three prime right to the very end of this double stranded piece of that DNAto
1806 blunt end.
1807 [00:00:48.92] But on the lagging strand right here, you have to jump ahead, synthesize
1808 jump ahead, synthesize back.And now you can't jump ahead enough to synthesize back
1809 way to the previous thing. So just to erase this last drawing, how are you going to fill in
1810 region? Because we cannot jump ahead to synthesize back.And here in the bottom, this
1811 made in the little larger scale.
[00:01:23.38] The solution to this problem is a special enzyme, a 1812 protein RNAcomplex
1813 the telomerase. Telomerase is depicted, the protein part, is in green.And its RNA
1814 depicted in blue.
1815 [00:01:42.76] The problem that telomerase is tackling is filling in this overhang region
1816 lagging strand cannot fill in. It does that by actually making the template strand a little
1817 This molecule of RNAthat telomerase has acts as a template for additional sequence at
1818 telomere ends, putting down extra copies of the telomere repeats-- I'll say a bit about
that in a
1819 second-- so that you're extending the other chromosome, the other strand, now you can
put in an
1820 RNAprimer and fill this end in with the Okazaki fragment, getting it to at least the
1821 required for the original chromosome end.
1822 [00:02:38.28] Now, the telomere repeat sequence, these fragments that are repeated
1823 over again. Telomeres actually have thousands of copies of six base pairs. It's a
1824 The sequence is different in different organisms, but they function similarly. In humans,
the 1825 sequences is TTAGGG.
1826 [00:03:00.98] And these thousands of copies of the telomere repeat act as a molecular
1827 Telomerase, the enzyme, is only active in certain cells. They are active in embryonic
1828 in development when a human is just forming. They are active in stem cells, which have
1829 infinite renewal capability.And they are inappropriately activated in cancer cells. That's
1830 the adaptations cancer cells have made to achieve immortality.
1831 [00:03:35.12] In the rest of cells, meaning most of our adult cells, our chromosomes are
1832 getting filled in each time. And they're actually getting shorter each cell division. This
1833 of telomeres is what acts as a clock. Eventually, the telomeres get so short that a cell is
1834 able to divide.
1835 [00:03:57.58] These cells are called senescent.And they won't necessarily die, but they
1836 longer divide. They are just present. You may have heard that you do not make new
1837 longer. These are an example of cells that are senescent.
1838 [00:04:21.46] This slide shows some of the details of the RNAtemplate. In this
1839 organism, the hexanucleotide repeat is a little different from human's, TTGGGG.And
1840 going to add that over and over again.
1841 [00:04:37.67] Now, one thing to consider is, how frequently would you expect a repeat
1842 How often would you expect a hexanucleotide to repeat? Since you can have four bases
1843 position-- you can have four bases at position one, four bases at position two, four bases
1844 position three. For a hexamer, that would be 4e6 .
1845 [00:05:02.13] Or you would expect any particular hexamer to occur once every 4,096
1846 Obviously here it's occurring every six basis, so that's statistically highly improbable if
1847 due to chance. But generally, it's something you need to know about, is to calculate how
1848 frequently you would expect to observe