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REV7 functions with REV3 as a checkpoint protein delaying mitotic entry until DNA replication is completed
Katarzyna Sobkowiak1, Masaoki Kohzaki1, Raphael Böhm2
1Department of Molecular and Cellular Biology, University of Geneva, 1205 Geneva, Switzerland.
Cell Reports
|March 19, 2025
Summary
REV7 protein inhibits cell division during DNA replication stress. This DNA repair protein
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- REV7 (MAD2B/MAD2L2) is a subunit of DNA polymerase zeta and the 53BP1-shieldin complex at DNA breaks.
- REV7 shares sequence similarity with the MAD2 spindle assembly checkpoint protein.
Purpose of the Study:
- To investigate the potential checkpoint function of REV7.
- To understand REV7's role in response to DNA replication stress.
Main Methods:
- Studied chicken and human cells exposed to DNA replication-stress agents.
- Examined REV7's function with and without inhibition of the ATR checkpoint.
- Analyzed REV7's ligand binding and homodimerization capabilities.
- Assessed mitotic entry in REV7 gene-deleted cells.
Main Results:
- REV7 inhibits mitotic entry in cells under replication stress, particularly when the ATR checkpoint is inhibited.
- REV7 exhibits ligand-dependent conformational changes and requires homodimerization for its checkpoint function.
- REV7 gene deletion causes premature mitotic entry even in unstressed cells.
Conclusions:
- REV7 possesses a DNA replication stress checkpoint function.
- REV7 may monitor ongoing DNA replication to prevent premature cell division.
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