GENOME STABILITY IN RAD MUTANTS
Principal Investigator: ADAM BAILIS
Abstract: Homologous recombination is an important pathway for the repair of DNA damage by radiation, chemicals, and endogenous cellular processes. However, recombination must be carefully controlled as deleterious genome rearrangements can result from unrestricted recombination between numerous, dispersed repetitive sequences. Since the majority of these repeats are 300 bp or shorter in eukaryotes, the control of recombination between these short sequences is more stringent than for longer sequences. Several of the genes known to mediate the response to radiation in the budding yeast S. cerevisiae also control short-sequence recombination (SSR). The goal of the proposed research program is to further investigate important interactions between several of the most critical factors at the genetic and molecular levels. DNA fragment insertion assays in cells with mutant SSR factors will be used to explore the effect of specific defects, both alone and in combination, on SSR. Repair of a genomic double-strand break by recombination will be used to monitor the kinetics of SSR in these mutants. Ligation mediated PCR will be employed to track and quantitate secondary breaks created during SSR. Chromatin immunoprecipitation will be used to follow the interaction of several important protein complexes and the recombination substrates. This combination of genetic and physical methods will promote a more thorough understanding of several of the molecular interactions critical for SSR, and the maintenance of genome stability.
Funding Period: 1998-05-01 - 2008-04-30
more information: NIH RePORT
- Telomere dysfunction drives increased mutation by error-prone polymerases Rev1 and zeta in Saccharomyces cerevisiaeDamon H Meyer
Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010 0269, USA
Genetics 175:1533-7. 2007..The increase was dependent on error-prone polymerases required for the mutagenic response to DNA lesions that block the replication fork...
- RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiaeNicholas R Pannunzio
Division of Molecular Biology, Beckman Research Institute of the City of Hope, 1500 E Duarte Road, Duarte, CA 91010 0269, United States
DNA Repair (Amst) 7:788-800. 2008..The high frequency of these events suggests that SSA may be an important mechanism of genome rearrangement following acute radiation exposure...
- Mating type influences chromosome loss and replicative senescence in telomerase-deficient budding yeast by Dnl4-dependent telomere fusionDamon H Meyer
Division of Molecular Biology, Beckman Research Institute of the City of Hope, and City of Hope Graduate School of Biological Sciences, Duarte, CA 91010 0269, USA
Mol Microbiol 69:1246-54. 2008....
- Telomerase deficiency affects the formation of chromosomal translocations by homologous recombination in Saccharomyces cerevisiaeDamon H Meyer
Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA
PLoS ONE 3:e3318. 2008..Thus, telomerase may exert a substantial effect on global genome stability, which may bear significantly on the appearance and progression of cancer in humans...
- Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiaeGlenn M Manthey
Division of Molecular Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, United States of America
PLoS ONE 4:e7488. 2009..These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage...