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

Authors

Alissa D Clear, Beckman Research Institute of City of Hope
Glenn M Manthey, Beckman Research Institute of City of Hope, bioStrategies Group
Olivia Lewis, Duarte High School NIH Science Education Partnership Award Program, Barbara Bush Houston Literacy Foundation
Isabelle Y Lopez, Duarte High School NIH Science Education Partnership Award Program, California State Polytechnic University at Pomona
Rossana Rico, Duarte High School NIH Science Education Partnership Award Program, University of California at Los Angeles
Shannon Owens, Beckman Research Institute of City of Hope, University of California at Davis
M Cristina Negritto, Pomona College
Elise W Wolf, Pomona College, University of California at San Francisco
Jason Xu, Pomona College, University of Pennsylvania
Nikola Kenjić, University of California at Riverside
J Jefferson P Perry, University of California at Riverside
Aaron W Adamson, Beckman Research Institute of City of Hope
Susan L Neuhausen, Beckman Research Institute of City of Hope
Adam M Bailis, Thomas Jefferson University, eckman Research Institute of City of HopeFollow

Document Type

Article

Publication Date

7-20-2020

Comments

This is the final published version of the article published in the journal Microbial Cell, 2020 Jul 20;7(10):270-285.

The article can also be found at the publishers website: https://doi.org/10.15698/mic2020.10.732.

Copyright. The Authors.

Abstract

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.

Recommended Citation

Clear, Alissa D; Manthey, Glenn M; Lewis, Olivia; Lopez, Isabelle Y; Rico, Rossana; Owens, Shannon; Negritto, M Cristina; Wolf, Elise W; Xu, Jason; Kenjić, Nikola; Perry, J Jefferson P; Adamson, Aaron W; Neuhausen, Susan L; and Bailis, Adam M, "Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast" (2020). College of Health Professions Faculty Papers. Paper 1.
https://jdc.jefferson.edu/jchpfp/1

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English