# The Role of Chromatin in the Repair of Radiation-Induced Damage

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $40,691

## Abstract

SUMMARY
DNA double-strand breaks (DSBs) are fundamental threats to genomic integrity that result in genomic
instability if not properly repaired, which can in turn lead to cancer and cell death. Although we know a great
deal about the pathways of DSB repair, we know very little about how DSB repair occurs in its natural
context in the cell, that is, chromatin. Chromatin by its very nature is an impediment for proteins accessing
the DNA, yet the repair machinery is somehow able to navigate through the chromatin and successfully
repair DNA damage. Chromatin also plays a key role in transducing the cell's response to DNA damage via
the DNA damage cell cycle checkpoint. Until recently, there has been a large gap in our understanding as to
how the DSB repair and the DNA damage checkpoint are influenced by the chromatin environment in
mammalian cells. Integral to this process is the progression of the DNA repair machinery along a genome
that is packaged into chromatin; how this occurs and the influence on the epigenome, has been a long-
standing mystery. We have recently shown that chromatin is completely disassembled and reassembled
during non-homologous end joining of double-strand DNA breaks in human cells. Excitingly, our recent
preliminary data strongly supports an active role for dynamic chromatin assembly onto single stranded DNA
(ssDNA) in the midst of homologous recombination-driven repair of DSBs as an intrinsic step required for
DSB repair. Histones occupying ssDNA has never been reported previously in vivo, let alone their playing an
important biological role. The proposed studies will uncover the nature of the histone-DNA complexes on
ssDNA, and will reveal the elusive mechanism whereby chromatin assembly promotes DSB repair in human
cells. By elucidating the mechanism whereby ssDNA-histone complexes contribute to DSB repair, we hope
to fill significant gaps in our current knowledge of the chromosomal repair process.

## Key facts

- **NIH application ID:** 10132269
- **Project number:** 5F31CA239442-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Faith Fowler
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,691
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132269

## Citation

> US National Institutes of Health, RePORTER application 10132269, The Role of Chromatin in the Repair of Radiation-Induced Damage (5F31CA239442-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132269. Licensed CC0.

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