# Molecular Modulator of RPA and RAD51 in Maintaining Genome Stability

> **NIH NIH R01** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2023 · $115,000

## Abstract

DNA damage constitutes a major threat to genetic integrity, and has thus been implicated in the
pathogenesis of cancer. Elucidating the mechanism safeguarding genome stability is important for
understanding the mechanism underlying carcinogenesis. Genome integrity is constantly threatened by
endogenous and exogenous agents arising from cellular metabolic processes as well as environmental
exposure, many of which impede normal DNA replication and cause replication fork stalling. Stalled forks need
to be properly repaired and rescued to prevent DNA lesions and genome instabilities that contribute to
tumorigenesis. To repair and rescue stalled replication, a network of proteins regulating DNA damage
response, DNA repair, replication, and cell cycle checkpoints are activated in response to stalled replication in
order to stabilize and restart stalled forks. However, the mechanism underlying fork repair is poorly understood.
Recent studies have revealed that the balance and dynamics of RAD51 and RPA at stalled forks are crucial for
fork stabilization and restart. Yet how RAD51 and RPA activities are modulated remains largely elusive. Our
recent findings suggest that the high-affinity single-stranded DNA binding protein complex known as CST may
be a new modulator for RPA and RAD51 at GC-rich repetitive sequences in response to replication stress. The
objective of this proposal is to understand the molecular relationship between CST, RAD51 and RPA in fork
rescue, with the goal to provide novel insights into how cells counteract DNA damage caused by genotoxins.
We propose to integrate advanced biochemical, cell biological, cell imaging, and next-gen sequencing
techniques to examine how CST may regulate RPA binding at stalled sites and maintain fork progression and
stability under stress (Aim 1), define how CST may modulate RAD51 activity at GC-rich stalled sites (Aim 2),
and characterize the regulatory role of a surface-exposed region of CST in regulating RAD51 and RPA
activities (Aim 3). Findings from the proposed research will provide novel information on the mechanism of
genome stability maintenance of rescuing stalled replication and preserving genome stability.

## Key facts

- **NIH application ID:** 11043815
- **Project number:** 7R01CA234266-07
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** Weihang Chai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $115,000
- **Award type:** 7
- **Project period:** 2019-12-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11043815

## Citation

> US National Institutes of Health, RePORTER application 11043815, Molecular Modulator of RPA and RAD51 in Maintaining Genome Stability (7R01CA234266-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11043815. Licensed CC0.

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