PCL477H1-Lecture 5b to post [Compatibility Mode]

PCL477H1-Lecture 5b to post [Compatibility Mode] - Two...

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Two major pathways for DSB-repair in eukaryotes homologous recombination (HR) -information from homologous chromosome used as template to fix DSB -involves exchange of segments of DNA a recombination via recombination non-homologous end joining (NHEJ) - joining of two ends of DNA without utilizing homologous template Differences: • HR main pathway (yeast) vs. NHEJ is main pathway (mammals) ? •c e ll cycle phase: NHEJ mainly in G0/G1 whereas HR occurs during late S and G2 phases • HR relatively error-free vs. NHEJ relatively error-prone
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The Szostak DSB Repair Model dashed lines: ewly synthesized DNA newly synthesized DNA (A+B) (A + b)
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Variations on this theme Synthesis-dependent strand annealing Mus81-dependent pathway
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Cohesion during HR established at replication origin
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X-ray sensitive hamster cell mutants defective in DSB-repair • XRCC series: genes found to restore defects (by functional complementation) in mutant hamster cells that have problems with repairing double-strand breaks • XRCC1: ? • XRCC2: HR XRCC3: HR • XRCC4: NHEJ RCC5: NHEJ XRCC5 NHEJ • XRCC6: NHEJ • XRCC7: NHEJ
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Proteins involved in Homologous Recombination DSB repair
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ingle – trand annealing (SSA) Single strand annealing (SSA) Homology-driven process but not homologous recombination •r e joining DSBs using homology between ends of joined sequences •D N A s t o b e joined are resected to produce complementary single strand DNA tails, annealing occurs at homologous sequence and the ssDNA overhangs immed by unknown process trimmed by unknown process end result is net loss of DNA sequence in S. cerevisiae, the Rad52 rotein probably binds DNA protein probably binds DNA ends, contributes to DNA annealing Rad50, Mre11, Nbs1 proteins robably responsible for probably responsible for resecting DNA ends
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adiation- duced subnuclear ‘foci’ Radiation induced subnuclear foci
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This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto.

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PCL477H1-Lecture 5b to post [Compatibility Mode] - Two...

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