DNA Replication When? • S (synthesis) phase of cell cycle • Creates copy of DNA and two copies are held together by centromere. • Thousands of times per second throughout the body. Where? • Always in the nucleus of eukaryotic cells. • All cells that are not in G0 phase (no longer dividing). Why? • When cells divide through meiosis or mitosis, new cells need their own DNA. How? • Two different mechanisms: lagging strand and leading strand, but always in the 5’ to 3’ direction. • Eukaryotic chromosomes average about 150 million nucleotides, so multiple replication forks are needed to finish the job. • Semi-conservative Key enzymes • • • • Topoisomerases unknot the DNA. Helicase unzips the DNA RNA primase adds RNA primer DNA polymerase adds nucleotides, repairs mismatch pairs, and removes the RNA primer • DNA ligase seals the okazaki fragments together by creating phosphodiester bonds. Proofreading • 1/1,000,000,000 nucleotides end up being incorrectly copied, however the original number is closer to 1/10,000. • During replication, DNA Polymerase finds mismatched pairs and fixes them. • There are many other proteins that also proofread the mistakes. Telomeres • The 5’ ends of daughter strands can never be fully completed due to the 5’ to 3’ direction. • Telomeres are DNA sections at the 5’ end of a chromosome that do not carry genes. • Telomerase is an enzyme with RNA that adds to the telomeres as the wear down through many rounds of replication. • Telomerase is only found in gamete producing cells as newborns need long telomeres. • Limitations on the life span of cells is based on the length of the telomeres. Cancer • Cancer cells divide very quickly and often, so telomerase activity is need to keep the telomeres from getting too small. • Telomerase activity is found in about 90% of all cancers.