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.