RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells

Nucleic Acids Research
Jennifer M MasonDouglas K Bishop

Abstract

The RAD54 family DNA translocases have several biochemical activities. One activity, demonstrated previously for the budding yeast translocases, is ATPase-dependent disruption of RAD51-dsDNA binding. This activity is thought to promote dissociation of RAD51 from heteroduplex DNA following strand exchange during homologous recombination. In addition, previous experiments in budding yeast have shown that the same activity of Rad54 removes Rad51 from undamaged sites on chromosomes; mutants lacking Rad54 accumulate nonrepair-associated complexes that can block growth and lead to chromosome loss. Here, we show that human RAD54 also promotes the dissociation of RAD51 from dsDNA and not ssDNA. We also show that translocase depletion in tumor cell lines leads to the accumulation of RAD51 on chromosomes, forming complexes that are not associated with markers of DNA damage. We further show that combined depletion of RAD54L and RAD54B and/or artificial induction of RAD51 overexpression blocks replication and promotes chromosome segregation defects. These results support a model in which RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in human tumor cells. Thus, in addition to having genome-sta...Continue Reading

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Citations

Feb 21, 2016·Pharmacology & Therapeutics·Navnath S GavandeJohn J Turchi
Feb 6, 2017·The Plant Journal : for Cell and Molecular Biology·Takeshi HirakawaSachihiro Matsunaga
Sep 29, 2019·Nature Communications·Jennifer M MasonDouglas K Bishop
Dec 24, 2019·Frontiers in Genetics·Beatriz Andrea Otálora-OtáloraAdriana Rojas
Sep 25, 2017·Frontiers in Microbiology·Andrew A KelsoMichael G Sehorn
Mar 13, 2019·Annual Review of Biophysics·J Brooks Crickard, Eric C Greene
Jul 8, 2020·Seminars in Cell & Developmental Biology·Alexander Carver, Xiaodong Zhang
Sep 10, 2018·DNA Repair·J Brooks Crickard, Eric C Greene
Jul 23, 2021·Current Opinion in Genetics & Development·John Brooks Crickard
Aug 4, 2021·Current Opinion in Genetics & Development·Diedre ReitzDouglas K Bishop

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Methods Mentioned

BETA
light microscopy
immunoprecipitation
transfection
DNA assay
electrophoretic mobility shift assay
electrophoresis

Software Mentioned

ImageJ
LSM software

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