Faculty, Staff and Student Publications
Publication Date
1-20-2025
Journal
Nature Communications
Abstract
Cells undergo tens of thousands of DNA-damaging events each day. Defects in repairing double-stranded breaks (DSBs) can lead to genomic instability, contributing to cancer, genetic disorders, immunological diseases, and developmental defects. Cohesin, a multi-subunit protein complex, plays a crucial role in both chromosome organization and DNA repair by creating architectural loops through chromatin extrusion. However, the mechanisms by which cohesin regulates these distinct processes are not fully understood. In this study, we identify two separate roles for cohesin in DNA repair within mammalian cells. First, cohesin serves as an intrinsic architectural factor that normally prevents interactions between damaged chromatin. Second, cohesin has an architecture-independent role triggered by ATM phosphorylation of SMC1, which enhances the efficiency of repair. Our findings suggest that these two functions work together to reduce the occurrence of translocations and deletions associated with non-homologous end joining, thereby maintaining genomic stability.
Keywords
Chromosomal Proteins, Non-Histone, Cell Cycle Proteins, DNA Breaks, Double-Stranded, Cohesins, Humans, Phosphorylation, Ataxia Telangiectasia Mutated Proteins, Chromatin, Genomic Instability, DNA Repair, Animals, DNA End-Joining Repair, Mice
DOI
10.1038/s41467-025-56086-4
PMID
39833168
PMCID
PMC11747280
PubMedCentral® Posted Date
1-20-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons