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Sir2 is part of this complex that binds to deacetylated histone tails * Chromosome Parts - Origins, Centromeres, Telomeres Every chromosome has to contains one centromere, two telomeres, and multiple origins of replication Every chromosome has multiple origins of replication. These origins fire only once per cell cycle Euchromatic and Heterochromatic regions replicate at different times during S phase. Euchromatin - early Heterochromatin - late Every chromosome has to contains one centromere, two telomeres, and multiple origins of replication Centromeres are required for the segregation of chromosomes during mitosis Mitotic chromosome condensation is driven by ATPases called Condensins Organization of a Centromere Centromeric Heterochromatin contains special nucleosomes =CENP-A Every chromosome has to contains one centromere, two telomeres, and multiple origins of replication Chromosome Ends are specialized structures called Telomeres Blue = chromosomes White = Telomere protein Repeated G rich sequence on one strand in humans: (TTAGGG)n Repeats can be several thousand basepairs long. In humans, telomeric repeats average 5-15 kilobases Telomere specific proteins, eg. TRF1 TRF2 bind to the repeat sequence and protect the ends Without these proteins, telomeres are acted upon by DNA repair pathways leading to chromosomal fusions Telomeres The End Replication Problem The end replication problem leads to loss of information from opposite strands at both ends 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ + 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ + 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ + + 5’ 3’ 5’ 3’ + Without some form of correction the end replication problem leads to the loss of 50-100 nucleotides from the newly synthesized lagging strand at each chromosome end in each round of duplication In mammalian (and many other) cells, the solution to this problem is that chromosome ends have a special duplication machinery = Telomerase Different types of Nucleotide Polymerases DNA
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