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Decoding replication stress responses through post-translational modifications
Jinhua Han1, Mengjie Wu2, Ting Liu3,4
1Zhejiang Key Laboratory of Geriatrics and Geriatrics Institute of Zhejiang Province, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nature Chemical Biology
|October 7, 2025
Summary
Cells use complex DNA replication stress responses to maintain genomic stability. Post-translational modifications (PTMs) are key regulators of these pathways, ensuring accurate DNA duplication under genotoxic conditions.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA replication is essential for cell division but faces challenges that threaten genomic integrity.
- Cells possess intricate stress response mechanisms to protect the genome during replication.
- Post-translational modifications (PTMs) are crucial for regulating these stress responses.
Purpose of the Study:
- To review the mechanisms cells use to respond to replication stress.
- To highlight the role of PTMs in regulating DNA replication fork dynamics.
- To discuss both histone and nonhistone PTMs in maintaining genomic stability.
Main Methods:
- Literature review of cellular responses to replication stress.
- Analysis of the role of PTMs in DNA replication and repair pathways.
- Synthesis of current research on histone and nonhistone modifications.
Main Results:
- Replication stress triggers various protective pathways like checkpoints and fork remodeling.
- PTMs dynamically control protein function, stability, and localization in stress responses.
- Both histone and nonhistone PTMs are critical for precise regulation of replication forks.
Conclusions:
- Cellular responses to replication stress are complex and essential for genomic stability.
- PTMs play a vital, dynamic role in orchestrating these responses.
- Further research into PTMs offers insights into maintaining genome integrity under stress.
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