Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast.

Autor:	Clear AD; Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA.; Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.; bioStrategies Group, Chicago, IL, USA., Manthey GM; Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA.; Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA., Lewis O; City of Hope - Duarte High School NIH Science Education Partnership Award Program, Duarte, CA, USA.; Barbara Bush Houston Literacy Foundation, Houston, TX, USA., Lopez IY; City of Hope - Duarte High School NIH Science Education Partnership Award Program, Duarte, CA, USA.; California State Polytechnic University at Pomona, Pomona, CA, USA., Rico R; City of Hope - Duarte High School NIH Science Education Partnership Award Program, Duarte, CA, USA.; Henry Samueli School of Engineering and Applied Sciences, University of California at Los Angeles, Los Angeles, CA, USA., Owens S; Eugene and Ruth Roberts Summer Student Academy, Beckman Research Institute of City of Hope, Duarte, CA, USA.; Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California at Davis, Davis, CA, USA., Negritto MC; Molecular Biology Program, Pomona College, Claremont, CA, USA., Wolf EW; Molecular Biology Program, Pomona College, Claremont, CA, USA.; Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA, USA., Xu J; Molecular Biology Program, Pomona College, Claremont, CA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kenjić N; Department of Biochemistry, University of California at Riverside, Riverside, CA, USA., Perry JJP; Department of Biochemistry, University of California at Riverside, Riverside, CA, USA., Adamson AW; Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA., Neuhausen SL; Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA., Bailis AM; Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA.; Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.; College of Health Professions, Thomas Jefferson University, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	Microbial cell (Graz, Austria) [Microb Cell] 2020 Jul 20; Vol. 7 (10), pp. 270-285. Date of Electronic Publication: 2020 Jul 20.
DOI:	10.15698/mic2020.10.732
Abstrakt:	RAD52 is a structurally and functionally conserved component of the DNA double-strand break (DSB) repair apparatus from budding yeast to humans. We recently showed that expressing the human gene, HsRAD52 in rad52 mutant budding yeast cells can suppress both their ionizing radiation (IR) sensitivity and homologous recombination repair (HRR) defects. Intriguingly, we observed that HsRAD52 supports DSB repair by a mechanism of HRR that conserves genome structure and is independent of the canonical HR machinery. In this study we report that naturally occurring variants of HsRAD52 , one of which suppresses the pathogenicity of BRCA2 mutations, were unable to suppress the IR sensitivity and HRR defects of rad52 mutant yeast cells, but fully suppressed a defect in DSB repair by single-strand annealing (SSA). This failure to suppress both IR sensitivity and the HRR defect correlated with an inability of HsRAD52 protein to associate with and drive an interaction between genomic sequences during DSB repair by HRR. These results suggest that HsRAD52 supports multiple, distinct DSB repair apparatuses in budding yeast cells and help further define its mechanism of action in HRR. They also imply that disruption of HsRAD52-dependent HRR in BRCA2-defective human cells may contribute to protection against tumorigenesis and provide a target for killing BRCA2-defective cancers. Competing Interests: Conflict of interest: The authors declare that there are no conflicts of interest. (Copyright: © 2020 Clear et al.)
Databáze:	MEDLINE
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