Lecture22S11 - BIS101/Engebrecht Lecture22 5/20/11 DNA...

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BIS101/Engebrecht Lecture22 5/20/11 DNA Repair: We saw yesterday that most pathways to repair DNA rely on 1) recognition of the damage/mismatch; 2) removal of the area surrounding the damage/mismatch; and 3) using the other strand as template to fill in the gap and religate to generate an intact DNA molecule. What happens if both strands are damaged? How does the cell repair this type of damage? Lets consider a break in the DNA molecule that interrupts both strands (a double strand break or DSB). In most somatic cells this would be repaired by nonhomologous end joining (NHEJ). This requires a number of proteins that recognize the break, bind and protect the ends, clean up the ends to provide the 5’P and 3’OH for DNA ligase to then glue together. What do you predict is the consequence of such a break? MUTATION. This mode of repair occurs primarily in the G0 or G1 phase of the cell cycle where there is no sister chromatid as a template for repair. However, if there is a sister chromatid, then cells can use homologous recombination to repair a break. When would breaks be encountered? 1) DNA replication- I drew a picture of a replication fork and showed you that if a nick (a break in a single strand of DNA) in the template strand is encountered replication will be blocked and you have a double strand break in the DNA. This must be repaired before DNA replication can proceed. 2) Physical (Xrays) and chemical (MMS) agents can cause double strand breaks by their mode of action. Recombination can play an important role in healing such breaks. Mutants in recombination proteins tend to be sick, have low fertility and may have a “mutator” phenotype. The primary mechanism for repairing DSBs with homologous recombination is SDSA: Synthesis-dependent strand annealing . The DSB undergoes end processing (5 3 exonuclease), followed by strand invasion, mediated by RecA/Rad51. This protein forms a filament on the single strand DNA exposed during resection. This filament invades the sister chromatid, resulting in displacement of the original strand (to form a D loop) and the formation of heteroduplex (duplex formation between the two different DNA molecules of the sister chromatids). The 3’ ends will serve a substrate for DNA polymerase, resulting in new DNA synthesis. This structure is then disrupted by unwinding and annealing back to the original DNA strands. Finally DNA ligase will reform two intact DNA molecules. The other time when homologous recombination is used is during meiosis.
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This note was uploaded on 06/05/2011 for the course BIS 101 taught by Professor Simonchan during the Spring '08 term at UC Davis.

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Lecture22S11 - BIS101/Engebrecht Lecture22 5/20/11 DNA...

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