Homologous recombination is an important biological response to DNA damage by radiation and chemicals. However, recombination must be controlled because deleterious genome rearrangements results from recombination between repeated sequences. Observations in several eukaryotic systems have established the recombination between sequences under 250 bp in length is tightly controlled. This is essential for the maintenance of genome stability because the majority of repeated sequences are short. In this laboratory, several radiation sensitivity (RAD) genes have been shown to control recombination between short sequences in the yeast S. cerevisiae, and that this control is distinct from the control of recombination between longer sequences. The further investigation of this selective control is the goal of the proposed research program. Novel deletion and translocation assays will be employed to determine the role of additional RAD genes in the control of short-repeat recombination (SRR). The role of these genes in double- strand break (DSB) processing, heteroduplex formation, and joint molecular formation during SRR will be analyzed with a novel DSB induced gene replacement assay. Together these genetic and physical studies will provide unique insight into how genomic integrity is maintained in the wake of DNA damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057484-04
Application #
6386884
Study Section
Radiation Study Section (RAD)
Program Officer
Anderson, Richard A
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
4
Fiscal Year
2001
Total Cost
$248,592
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010
Sheldon, Kathryn E; Shandilya, Harish; Kepka-Lenhart, Diane et al. (2013) Shaping the murine macrophage phenotype: IL-4 and cyclic AMP synergistically activate the arginase I promoter. J Immunol 191:2290-8
Pannunzio, Nicholas R; Manthey, Glenn M; Bailis, Adam M (2010) RAD59 and RAD1 cooperate in translocation formation by single-strand annealing in Saccharomyces cerevisiae. Curr Genet 56:87-100
Manthey, Glenn M; Bailis, Adam M (2010) Rad51 inhibits translocation formation by non-conservative homologous recombination in Saccharomyces cerevisiae. PLoS One 5:e11889
Manthey, Glenn M; Naik, Nilan; Bailis, Adam M (2009) Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae. PLoS One 4:e7488
Meyer, Damon H; Bailis, Adam M (2008) Telomerase deficiency affects the formation of chromosomal translocations by homologous recombination in Saccharomyces cerevisiae. PLoS One 3:e3318
Meyer, Damon H; Bailis, Adam M (2008) Mating type influences chromosome loss and replicative senescence in telomerase-deficient budding yeast by Dnl4-dependent telomere fusion. Mol Microbiol 69:1246-54
Pannunzio, Nicholas R; Manthey, Glenn M; Bailis, Adam M (2008) RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae. DNA Repair (Amst) 7:788-800
Meyer, Damon H; Bailis, Adam M (2007) Telomere dysfunction drives increased mutation by error-prone polymerases Rev1 and zeta in Saccharomyces cerevisiae. Genetics 175:1533-7
Manthey, Glenn M; Bailis, Adam M (2002) Multiple pathways promote short-sequence recombination in Saccharomyces cerevisiae. Mol Cell Biol 22:5347-56