# Chromatin's Role in Repair of Radiation-induced Damage

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $322,050

## Abstract

SUMMARY
Radiation-induced 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 recombinational 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:** 10056195
- **Project number:** 5R01CA095641-17
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Jessica K Tyler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $322,050
- **Award type:** 5
- **Project period:** 2002-05-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056195

## Citation

> US National Institutes of Health, RePORTER application 10056195, Chromatin's Role in Repair of Radiation-induced Damage (5R01CA095641-17). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10056195. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*