Heyer Lab
Principal Investigator: Wolf-Dietrich Heyer
Institution: University of California, Davis (Davis, CA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Hiring Postdocs
Research Focus
Project Summary The general goal of the proposed research is to define the mechanistic underpinning for the synthetic lethality network between a deficiency in homologous recombination (HR) and defects in single-strand annealing (RAD52) or POLq-mediated end-joining (TMEJ). Exciting preliminary data revealed that BRCA2 and RAD52 delay the repair of S-phase-associated DNA double-stranded breaks (DSB) by TMEJ until M-phase. This regulation avoids TMEJ-mediated chromosomal rearrangements of one-sided DSBs that are produced by replication fork breakage. Our approach combines innovative cell cycle phase resolved imaging of DNA repair proteins and DNA damage markers with mechanistic biochemical analysis using purified human proteins in reconstituted reactions. Our results will have potential translational implications for the clinical application of newly developed RAD52 and POLq inhibitors for the treatment of HR-deficient tumors with respect to application protocols, patient selection, and use of DNA damage response checkpoint inhibitors as well as the response to poly(ADP-ribose) polymerase inhibition. The Specific Aims are: 1. Define the mechanism of action of BRCA2 in DSB repair path…
Active NIH Awards
- 5R01CA273911-04: Regulation of DNA double-strand break repair pathway choice (2026)
- 5R35GM157976-02: Mechanisms of Recombinational DNA Repair (2026)
- 2P30CA093373-24: Integrated Cancer Biology Program (2026)
- 5R01CA273911-03: Regulation of DNA double-strand break repair pathway choice (2025)
- 5R01GM058015-24: Recombinational Mechanisms of DNA Repair (2025)
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