# Role of homologous recombination in the replication stress response

> **NIH NIH R35** · CLEMSON UNIVERSITY · 2022 · $369,652

## Abstract

PROJECT SUMMARY/ABSTRACT
Precise replication of DNA is required to maintain genome stability. Replication forks face many obstacles from
both endogenous and exogenous sources that result in fork stalling or breakage threatening genome integrity.
The double strand break repair pathway, homologous recombination, has critical roles at stalled replication forks
independent of double strand break repair. The importance of this pathway is highlighted by patients with
inherited chromosomal instability orders and cancer predisposition syndromes. Although an intense area of
study, the mechanistic role of recombination proteins at replication forks is still poorly understood. A
comprehensive understanding of the replication response is critical for the understanding the molecular
mechanisms of human disease and to lead to development of novel therapeutics for patients harboring defects
in replication response genes. The long-term goal of the PI to elucidate the roles of recombination proteins in
the replication stress response. Here we will elucidate the role of recombination proteins at hydroxyurea-stalled
replication forks in two distinct projects. In Project 1, we use a powerful separation-of-function allele of the central
recombination enzyme, RAD51, to determine how RAD51 protects the integrity of the replication fork during
unchallenged and stressed conditions using a combination of genetic, molecular biology and proteomic
approaches. In Project 2, we propose a series of experiments to investigate the role of additional recombination
accessory factors in the replication response. Preliminary data from our lab has uncovered a novel role for
recombination proteins in protecting the integrity of stalled replication forks. We will test our current models
through mechanistic dissection of the replication stress response pathway using genetic and molecular
approaches. The work presented here will lay the foundation for future studies involving the elucidation of
molecular mechanisms of recombination proteins involved in the replication stress response. The completion of
this work will lead to not only a better of understanding of the role recombination proteins play at stalled
replication forks, but will also provide molecular insight into how disruption of this pathway results in human
disease. A complete understanding of this pathway is essential for development of therapeutics for patients with
inherited genome instability disorders and cancer that target the cellular replication response.

## Key facts

- **NIH application ID:** 10454945
- **Project number:** 5R35GM142512-02
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Jennifer Mason
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $369,652
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454945

## Citation

> US National Institutes of Health, RePORTER application 10454945, Role of homologous recombination in the replication stress response (5R35GM142512-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454945. Licensed CC0.

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