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Lecture 5

Cell Biology - Lecture 5 - Video 1.2 - Notes

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CAS BI 203
Martin Steffen

Lesson 5 – Video 1b [00:00:00.00] 1799 [00:00:01.53] PROFESSOR: We'll continue our discussion of DNAreplication with talking 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 stranded 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 section. 1804 And since you have the leading strand here, there'll be no problem synthesizing this from five 1805 prime to three prime right to the very end of this double stranded piece of that DNAto produce a 1806 blunt end. 1807 [00:00:48.92] But on the lagging strand right here, you have to jump ahead, synthesize back, 1808 jump ahead, synthesize back.And now you can't jump ahead enough to synthesize back all the 1809 way to the previous thing. So just to erase this last drawing, how are you going to fill in this 1810 region? Because we cannot jump ahead to synthesize back.And here in the bottom, this point is 1811 made in the little larger scale. 50 [00:01:23.38] The solution to this problem is a special enzyme, a 1812 protein RNAcomplex called 1813 the telomerase. Telomerase is depicted, the protein part, is in green.And its RNA component is 1814 depicted in blue. 1815 [00:01:42.76] The problem that telomerase is tackling is filling in this overhang region where the 1816 lagging strand cannot fill in. It does that by actually making the template strand a little longer. 1817 This molecule of RNAthat telomerase has acts as a template for additional sequence at the 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 distance 1821 required for the original chromosome end. 1822 [00:02:38.28] Now, the telomere repeat sequence, these fragments that are repeated over and 1823 over again. Telomeres actually have thousands of copies of six base pairs. It's a hexanucleotide. 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 clock. 1827 Telomerase, the enzyme, is only active in certain cells. They are active in embryonic cells early 1828 in development when a human is just forming. They are active in stem cells, which have this 1829 infinite renewal capability.And they are inappropriately activated in cancer cells. That's one of 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 not 1832 getting filled in each time. And they're actually getting shorter each cell division. This shortening 1833 of telomeres is what acts as a clock. Eventually, the telomeres get so short that a cell is no longer 1834 able to divide. 1835 [00:03:57.58] These cells are called senescent.And they won't necessarily die, but they can no 1836 longer divide. They are just present. You may have heard that you do not make new neurons any 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 particular 1839 organism, the hexanucleotide repeat is a little different from human's, TTGGGG.And we're 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 to occur? 1842 How often would you expect a hexanucleotide to repeat? Since you can have four bases in any 1843 position-- you can have four bases at position one, four bases at position two, four bases at 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 bases. 1846 Obviously here it's occurring every six basis, so that's statistically highly improbable if it were 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
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