# Regulation of Initial Steps of Chromosomal Breaks Repair

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $69,055

## 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:** 10611707
- **Project number:** 3R01GM125650-05S1
- **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:** $69,055
- **Award type:** 3
- **Project period:** 2018-01-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10611707

## Citation

> US National Institutes of Health, RePORTER application 10611707, Regulation of Initial Steps of Chromosomal Breaks Repair (3R01GM125650-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10611707. Licensed CC0.

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