Control of DNA Replication

Coolest DNA replication video ever! https://www.youtube.com/watch?v=4jtmOZaIvS0

Cell Cycle DNA synthesis take place in S Cell cycle progress enables initiation of replication of the genome by providing Cdc6 and Cdt1

Eukaryotic initiation of replication In yeast, 3 proteins needed to assemble the replisome ORC, Cdt1 and Cdc6 All three recruit helicase MCM complex mini-chromosome maintenance

The replication problem at the end of chromosomes

Telomeres in Tetrahymena Elizabeth Blackburn and Joe Gall, 1978 Single-celled ciliate Micronucleus Macronucleus Fragmented chromosomes 40,000 telomeres TTGGGG repeated sequence Telomerase, adds the short repeats to the 3’ ends of DNA

Telomere lengthening Telomerase = Protein + RNA Lengthening of the 3’ overhang Telomerase = Protein + RNA Telomerase anneals to the 3’ overhang Replication of complementary strand Telomerase Primer is synthesized Primase Elongation Polymerase fills in the gap DNA polymerase Translocation The primer is removed and ligase seals the gap Elongation

Telomeric cap structure Telomeres preserve chromosomal integrity by associating with proteins that form a protective cap Without cap, the double stranded ends would be mistaken as a ds break Can lead to apoptosis telomeric repeat binding factor WRN - helicase

Telomeres and Aging Somatic cells produce very little telomerase Chromosomes get shorter with each cell division Many Cancers have increased levels of telomerase Telomeres the Secret of Life!!! Dysfunctional telomeres and mutation in WRN gene Werner Syndrome Picture below same person at 15 and 48

Concept question The number of proteins in the prokaryotic replisome is 13, while the number in a eukaryotic cell is 27. What are the important protein components of the replisome in general? Why might a eukaryotic cell have more components?