fall 09 lecture 11cont-12intro

fall 09 lecture 11cont-12intro - The problem with...

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The problem with replicating linear molecules: Chromosomes lose about 100 base pairs from their 5’ ends in each mitosis genetic information is getting lost with time Leading strand is fine - continuous 5’-3’ elongation Lagging strand : when the final RNA fragment is removed from the 5’ end of the lagging strand, there is no upstream strand (available 3’OH) onto which DNA Pol I can build to fill the gap 3’ ends overhang - ss, unprotected
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Telomeres and telomerase : Telomere : the natural end of a linear chromosome DNA sequence consists of a simple repeating unit (6-7 nt) with a protruded single-stranded 3’ end that may fold into a loop human sequence is TTAGGG – forming a G-rich strand Telomerase : enzyme that repairs, replicates the ends of chromosomes ribonucleoprotein – protein-RNA complex carries its own little template RNA has reverse transcriptase activity (RNA →DNA) oker, 2005. Genetics Analysis & Principles, 2 nd ed)
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Telomerase – action/role 1. Polymerase extends primers in 5’-3’ direction, so it’s unable to copy extreme 3’ end of the lagging strand template after degradation of last primer→ 3’ overhang (=one telomeric repeat in the picture) 2. Enzyme telomerase - modified reverse transcriptase, carries RNA template, which is complementary to the telomeric repeats 3. Telomerase adds nucleotides to 3’ OH end of the lagging strand template to extend it – it polymerizes deoxyribonucleotides according to its own RNA template 4. Extends telomere region by one repeat unit 5. After elongation of 3’ end of the lagging strand template, new RNA primer for the lagging strand will be made by primase and polymerization will continue by polymerase 6. New RNA primer will be degraded; final result is an extra 3’ overhang of the lagging strand template One repeat unit Enzyme with template
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Something to think about : yeasts: unicellular Eu organisms, cells that proliferate indefinitely (as they have to reproduce) → possess homeostatic mechanisms to maintain telomere length within a limited range animal germ-line cells – similar human somatic cells - a different story: shortening of telomere length Telomerase generally found only in : unicellular eukaryotes (yeast, Tetrahymena thermophila ) germ cells, incl. embryonic stem (ES) cells cancer cells telomere length increases early in development – somatic cells are “born” with full complement of telomeric repeats some human cells do briefly express telomerase during S phase but telomerase is turned off in a tissue like skin (sometimes telomere length is maintained through DNA recombinations in telomere regions) There is an obvious link between presence of telomerase and maintenance of telomere length Possible role of telomerase in aging (as it is absent in mature tissues)?
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fall 09 lecture 11cont-12intro - The problem with...

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