# Studying the mechanisms underlying the protection of common fragile sites and structure-prone DNA sequences

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $389,402

## Abstract

Principal Investigator: Wu, Xiaohua
Project Summary
Studying the mechanisms underlying the protection of common fragile sites and structure-
prone DNA sequences
Project Summary/Abstract
 Common fragile sites (CFSs) are large chromosomal regions that often exhibit gaps and
breaks on metaphase chromosomes upon replication stress. Structure-prone AT-rich sequences
present at CFSs (CFS-ATs) contribute to CFS instability. Besides CFS-ATs, other structure-prone
DNA sequences, such as G-quadruplexes (G4s), are also abundant in the human genome and are
associated with chromosomal rearrangement breakpoints in cancer. Since CFSs and many
structure-prone DNA sequences, including G4s, are part of normal chromosomal structures, it is
important to understand how the integrity of these structure-prone DNA sequences is maintained in
mammalian cells. In this grant application, we will use EGFP-based DSB repair reporters to
investigate the mechanisms underlying the protection of structure-prone DNA sequences present at
CFSs and G4s. We will study the role of chromatin-remodeling in the maintenance of CFSs and
address the DSB repair mechanism specifically used to repair DSBs arising at DNA secondary
structures upon fork collapse. We will also explore the functional coordination of pathways involved
in protecting structure-prone DNA sequences from DSB formation and in repairing DSBs generated
upon fork collapse at structure-prone DNA sequences. Furthermore, we will study how mismatch
repair (MMR) proteins help preserve the integrity of structure-prone DNA sequences. Our studies
will yield molecular insights into the mechanisms underlying the maintenance of the integrity of CFS
and other structure-prone DNA sequences. These studies will also lay the groundwork for
development of new targeted cancer treatment strategies.

## Key facts

- **NIH application ID:** 10853005
- **Project number:** 5R01CA187052-09
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Xiaohua Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $389,402
- **Award type:** 5
- **Project period:** 2015-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853005

## Citation

> US National Institutes of Health, RePORTER application 10853005, Studying the mechanisms underlying the protection of common fragile sites and structure-prone DNA sequences (5R01CA187052-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10853005. Licensed CC0.

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