# Project 4 Gautier

> **NIH NIH P01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $359,493

## Abstract

SUMMARY
DNA double-strand break (DSB) repair is essential to prevent persistent DNA damage,
counteract genome instability and suppress tumor development. The spatial organization of
DNA repair is critical to protect the genome from chromosome translocations and complex
rearrangements. Thus, it is critical to better understand the mechanisms underlying the
formation of DNA repair domains and the contribution of these domains to the maintenance of
genome stability and, ultimately, tumor suppression. Armed with novel tools to manipulate the
formation of homology-directed repair domains, we propose three specific aims to assess the
impact of perturbing their formation on DNA repair and genome stability: mutation generation
and chromosome rearrangements. First, we will investigate further how actin movements
generated by the WASP-ARP2/3 pathway participate in DSB repair domain formation using
ARP2/3 inhibition or clinically relevant mutations in WASP. Repair domains will be probed by
state-of-the-art microscopy as well as by chromosome conformation capture assays (Hi-C).
Next, we will assess the consequences of interfering with DNA repair domain formation on
genome stability, specifically on chromosome translocations arising from various genomic
insults: endonucleases, topoisomerase inhibitors and replication stressors. Finally, we will
define the mutational signatures associated with DSB repair domain defects using loss and gain
of function mutations in the WASP-ARP2/3 pathway. This project will greatly benefit from
conceptual and technical interactions with all other projects of the program. The proposed
experiments should provide an unprecedented level of understanding of the impact of the
spatial organization of the nucleus, i.e. repair domains, on genome stability and subsequent
tumor development.

## Key facts

- **NIH application ID:** 9855794
- **Project number:** 2P01CA174653-06
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** JEAN GAUTIER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,493
- **Award type:** 2
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855794

## Citation

> US National Institutes of Health, RePORTER application 9855794, Project 4 Gautier (2P01CA174653-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9855794. Licensed CC0.

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