Histone H1 deamidation facilitates chromatin relaxation for DNA repair

Yuan Tian, Tingting Feng, Jun Zhang, Qingren Meng, Wenxin Zhan, Ming Tang, Chaohua Liu, Mengyan Li, Wenhui Tao, Yuxin Shu, Yu Zhang, Feng Chen, Shunichi Takeda, Qian Zhu, Xiaopeng Lu and Wei-Guo Zhu ()
Additional contact information
Yuan Tian: Shenzhen University Medical School
Tingting Feng: Shenzhen University Medical School
Jun Zhang: Shenzhen University Medical School
Qingren Meng: Shenzhen University Medical School
Wenxin Zhan: Shenzhen University Medical School
Ming Tang: Tongji University
Chaohua Liu: Fudan University
Mengyan Li: Shenzhen University Medical School
Wenhui Tao: Shenzhen University Medical School
Yuxin Shu: Wannan Medical College
Yu Zhang: Shenzhen University Medical School
Feng Chen: Shenzhen University Medical School
Shunichi Takeda: Shenzhen University Medical School
Qian Zhu: Shenzhen University Medical School
Xiaopeng Lu: Shenzhen University Medical School
Wei-Guo Zhu: Shenzhen University Medical School

Nature, 2025, vol. 641, issue 8063, 779-787

Abstract: Abstract The formation of accessible chromatin around DNA double-strand breaks is essential for their efficient repair1. Although the linker histone H1 is known to facilitate higher-order chromatin compaction2,3, the mechanisms by which H1 modifications regulate chromatin relaxation in response to DNA damage are unclear. Here we show that CTP synthase 1 (CTPS1)-catalysed deamidation of H1 asparagine residues 76 and 77 triggers the sequential acetylation of lysine 75 following DNA damage, and this dual modification of H1 is associated with chromatin opening. Mechanistically, the histone acetyltransferase p300 showed a preference for deamidated H1 as a substrate, establishing H1 deamidation as a prerequisite for subsequent acetylation. Moreover, high expression of CTPS1 was associated with resistance to cancer radiotherapy, in both mouse xenograft models and clinical cohorts. These findings provide new insights into how linker histones regulate dynamic chromatin alterations in the DNA damage response.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-08835-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:641:y:2025:i:8063:d:10.1038_s41586-025-08835-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-08835-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().