# Mechanism and Regulation of Homologous Recombination in Genome Maintenance

> **NIH NIH R35** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $396,250

## Abstract

Project Summary
DNA double-strand break (DSB) is one of the most toxic DNA lesions in cells. DSB causes
immediate chromosome breakage and must be repaired before chromosome segregation.
Unfaithful repair of DSB may lead to genome rearrangements and ultimately tumorigenesis.
Research in my laboratory strives to define the mechanism and regulation of DSB repair where
homologous recombination (HR) serves as a major repair means. Eukaryotic single-stranded
DNA binding protein, RPA, as a universal DNA replication and repair factor, is involved in
multiple stages of the HR pathway including the DSB end resection by the Sgs1-Dna2
helicase/nuclease ensemble. Our recent work discovered RPA as a processive unit for Dna2-
catalyzed ssDNA digestion, which provided a novel perspective on the regulation of ssDNA
accessibility by RPA and inspired us to explore how RPA may serve as an integral component
of the Sgs1-Dna2 machinery and coordinate their actions. Unexpectedly, our work on the Dna2-
RPA ensemble revealed a novel role of Dna2 in the processing of an undefined intermediate in
DSB repair likely derived from DNA repair synthesis and led us to discover an RPA mutant that
constitutively dimerizes, which may serve as a powerful tool to understand the function of RPA
dimerization. Both directions will also be explored in this proposal. Given the conservation of the
HR pathway between yeast and humans, our work will shed light on the mechanism of DSB
repair not only in yeast but also in human cells.

## Key facts

- **NIH application ID:** 10765058
- **Project number:** 1R35GM152207-01
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** HENGYAO NIU
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $396,250
- **Award type:** 1
- **Project period:** 2024-07-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765058

## Citation

> US National Institutes of Health, RePORTER application 10765058, Mechanism and Regulation of Homologous Recombination in Genome Maintenance (1R35GM152207-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10765058. Licensed CC0.

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