Our long-term goal is to understand the mechanisms of DMA repair process via recombination. DNA recombination repairs DNA double-strand breaks (DSBs) and gaps that occur spontaneously or are induced by chemicals or irradiation. The same type of DNA damage can be repaired by different pathways of recombination, depending on the cellular state. The decision as to which way to repair damage is crucial for cells to maintain genome stability. The objective of this project is to understand the mechanisms underlying the choice of recombination pathway in the model organism Saccharomyces cerevisiae. DNA repair processes are conserved in evolution, so the proposed research is highly relevant to our understanding of the mechanisms of DNA repair via recombination in humans. We used a new approach to identify important proteins involved in DNA recombination regulation. Fluorescence microscopy, chromatin immunoprecipitation and two-dimensional gel electrophoresis, we applied to study the mechanisms of recombination pathway choice and the function of proteins involved. We will define the mechanism of the cell cycle-regulated molecular switch between homologous and nonhomologous DSBs repair pathways. This study has important implications for new strategies for gene therapy in human cells. We have developed an assay to identify and characterize factors regulating choice of crossover and noncrossover recombination. Crossover pathway control is crucial to avoid loss of heterozygosity, genomic rearrangements in mitotic cycle and to prevent chromosome nondisjunction that causes aneuploidy (trisomy or monosomy) in meiotic cells. Aneuploidy is the most commonly identified chromosome abnormality in humans, occurring in at least 5% of all clinically recognized pregnancies and is the leading genetic cause of pregnancy loss. Mutations in genes encoding the proteins we study cause severe disorders in humans with increased predisposition to cancer. Therefore understanding their function, on the genetic and molecular levels is a critically important subject for human health. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM080600-01
Application #
7245956
Study Section
Molecular Genetics C Study Section (MGC)
Program Officer
Portnoy, Matthew
Project Start
2007-05-01
Project End
2012-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
1
Fiscal Year
2007
Total Cost
$280,770
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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Chen, Xuefeng; Niu, Hengyao; Yu, Yang et al. (2016) Enrichment of Cdk1-cyclins at DNA double-strand breaks stimulates Fun30 phosphorylation and DNA end resection. Nucleic Acids Res 44:2742-53
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