# Regulation of Recombinational DNA Repair

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $306,042

## Abstract

   
DESCRIPTION (provided by applicant): The general goal of the proposed research is to identify and define pathways that regulate homologous recombination as a DNA repair and DNA damage tolerance pathway in somatic cells. The fundamental approach is to use the budding yeast Saccharomyces cerevisiae as a lead organism and to establish novel mechanisms, which will be transferred by proof-of-principle experiments to humans to validate the general significance of the original paradigms. The Specific Aims are: 1. Determine the mechanism of anti-recombination and crossover regulation by Srs2. Srs2 is an anti- recombinase that acts by dissociating Rad51 from ssDNA. In addition, Srs2 has been demonstrated genetically to limit crossover formation. Sub-aim A: We will determine the mechanism of crossover regulation by Srs2. We will determine the roles of Rad55-Rad57 and PCNA and their post-translational modifications on the Srs2 anti-recombination and anti-crossover activity. Sub-aim B: We will extend these findings to humans and determine which proteins proposed to exert Srs2 function are involved in crossover control. 2. Determine the mechanism of activation of Mus81-Mms4. Mus81-Mms4 is a structure-selective endonuclease that processes HR-dependent joint molecules. We have reconstituted in vitro the Cdc5 (Polo kinase)-mediated activation of Mus81-Mms4 and developed an experimental plan to differentiate between different mechanistic models of direct activation of the Mus81-Mms4 catalytic activity. Sub-aim A: We will establish the mechanism of activation using genetic and biochemical approaches in yeast. Sub-aim B: We will conduct proof-of-principle experiments to show that also human MUS81-EME1 is directly activated by Polo- kinase-mediated phosphorylation.

## Key facts

- **NIH application ID:** 9897468
- **Project number:** 5R01CA092276-18
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Wolf-Dietrich Heyer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $306,042
- **Award type:** 5
- **Project period:** 2001-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897468

## Citation

> US National Institutes of Health, RePORTER application 9897468, Regulation of Recombinational DNA Repair (5R01CA092276-18). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9897468. Licensed CC0.

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