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The TONSL-MMS22L complex and FANCM form an interdependent complex on chromatin to counter replication stress
Haixia Zhou1,2, Jiaoyan Yan1,3,2, Xinlei Cao1,3,2
1Oncology Discipline Group, The Key Laboratory of Pediatric Hematology and oncology Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China.
Biorxiv : the Preprint Server for Biology
|October 1, 2025
Summary
The FANCM-TONSL-MMS22L complex resolves DNA replication stress by coordinating DNA repair pathways. This complex is crucial for maintaining genome stability and may be a therapeutic target in certain cancers.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- FANCM is a crucial DNA translocase for managing replication stress.
- The TONSL-MMS22L heterodimer interacts with histones and plays a role in DNA repair.
Purpose of the Study:
- To investigate the functional interplay between FANCM and TONSL-MMS22L during replication stress.
- To elucidate the role of the FANCM-TONSL-MMS22L complex in DNA repair and genome stability.
Main Methods:
- Chromatin immunoprecipitation assays
- Western blotting
- Analysis of DNA repair pathway activation
- Prognostic analysis in cancer patients
Main Results:
- Replication stress induces an interdependent FANCM-TONSL-MMS22L chromatin complex.
- This complex facilitates DNA interstrand crosslink (ICL) repair, homologous recombination, and replication fork stability.
- Low TONSL-MMS22L expression correlates with a better prognosis in wildtype FANCM cancer patients.
Conclusions:
- The FANCM-TONSL-MMS22L complex is essential for resolving replication stress and maintaining genome integrity.
- This complex acts coordinately on chromatin to promote DNA repair and suppress aberrant recombination.
- The FANCM-TONSL-MMS22L complex represents a potential therapeutic target for wildtype FANCM-associated cancers.
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