# Regulation of Initial Steps of Chromosomal Breaks Repair

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $329,600

## Abstract

Recombination is essential in maintaining genome stability, and even minor deficiency in recombinational
double-strand break (DSB) repair pathways results in cancer or other severe diseases. The initial processing of
DNA DSBs to single strands, a process termed DNA end resection, is the critical first step of homologous
recombination needed for the loading of damage response and repair proteins. Resection is tightly controlled in
the cell cycle and determines the usage of homologous recombination versus nonhomologous end joining for
repair. In yeast and human cells, the Mre11-Rad50-Nbs1/Xrs2 complex initiates resection, whereas Exo1 or
Sgs1-Dna2 mediates extensive resection. Systematic studies of resection have thus far only been done in
euchromatin, whereas we propose to study it in three different types of silenced heterochromatin. We designed
many new assays to examine resection within transcriptionally silent chromatin in fission yeast (Aim #1). The
fission yeast system provides an excellent model organism for this study as chromatin features are well
conserved with those in human cells. In Aim #2 we focus on control of one of the most mutagenic pathways of
DSB repair called Break Induced Replication (BIR). BIR is normally used for the repair of a single-end DSB. Here
the goal is to understand how this pathway is suppressed during the repair of two-ended DSBs. We focus on the
role of ssDNA annealing by Rad52 and synchronous resection of two ends of a DSB by the Mre11-Rad50-Xrs2
complex. In Aim #3 we focus on the resection-independent function of Dna2 nuclease/helicase during
homologous recombination.

## Key facts

- **NIH application ID:** 10364268
- **Project number:** 2R01GM125650-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Grzegorz A Ira
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $329,600
- **Award type:** 2
- **Project period:** 2018-01-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364268

## Citation

> US National Institutes of Health, RePORTER application 10364268, Regulation of Initial Steps of Chromosomal Breaks Repair (2R01GM125650-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10364268. Licensed CC0.

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