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Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair.
Nikolaos Parisis1,2,3,4, Pablo D Dans5,6,7, Muhammad Jbara8,9
1IGMM, CNRS, INSERM, University of Montpellier, Montpellier, France.
Nature Communications
|August 22, 2023
Summary
Researchers discovered histone H3 serine-57 phosphorylation (H3S57ph), a key modification crucial for DNA repair and recovery from replication stress across species. This finding reveals new insights into chromatin regulation and DNA damage response mechanisms.
Area of Science:
- Molecular Biology
- Epigenetics
- Genetics
Background:
- Histone post-translational modifications regulate chromatin structure and function.
- Phosphorylation is a critical but underrepresented histone modification.
- Understanding these modifications is key to comprehending DNA replication and repair.
Purpose of the Study:
- To report the discovery of histone H3 serine-57 phosphorylation (H3S57ph).
- To investigate the role of H3S57ph in DNA repair pathways and replication stress response.
- To identify the kinase responsible for H3S57ph in human cells.
Main Methods:
- Identification of H3S57ph using biochemical and genetic approaches.
- Characterization of H3S57ph function in DNA repair pathways in yeast and human cells.
- Analysis of replication stress recovery, DNA repair protein binding, and DNA repair pathway dependency.
Main Results:
- H3S57ph is conserved from fungi to vertebrates and is regulated by CHK1 kinase.
- Disrupting or mimicking H3S57ph impacts replication stress recovery, 53BP1 binding, and RAD52 dependency.
- H3S57ph modification loosens DNA-histone contacts, enhances nucleosome mobility, and interacts with H3K56.
Conclusions:
- Dynamic phosphorylation of H3S57 is essential for DNA repair and recovery from replication stress.
- H3S57ph plays a significant role in maintaining genome stability.
- This discovery opens new avenues for exploring histone modifications in DNA-related processes.
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