A dual role of Cohesin in DNA DSB repair
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...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56086-4 |
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| author | Michael Fedkenheuer Yafang Shang Seolkyoung Jung Kevin Fedkenheuer Solji Park Davide Mazza Robin Sebastian Hiroyuki Nagashima Dali Zong Hua Tan Sushil Kumar Jaiswal Haiqing Fu Anthony Cruz Supriya V. Vartak Jan Wisniewski Vittorio Sartorelli John J. O’Shea Laura Elnitski Andre Nussenzweig Mirit I. Aladjem Fei-Long Meng Rafael Casellas |
| author_facet | Michael Fedkenheuer Yafang Shang Seolkyoung Jung Kevin Fedkenheuer Solji Park Davide Mazza Robin Sebastian Hiroyuki Nagashima Dali Zong Hua Tan Sushil Kumar Jaiswal Haiqing Fu Anthony Cruz Supriya V. Vartak Jan Wisniewski Vittorio Sartorelli John J. O’Shea Laura Elnitski Andre Nussenzweig Mirit I. Aladjem Fei-Long Meng Rafael Casellas |
| author_sort | Michael Fedkenheuer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-473ed0a0d10f488f981030ce3a77c97e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-473ed0a0d10f488f981030ce3a77c97e2025-01-26T12:42:47ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-025-56086-4A dual role of Cohesin in DNA DSB repairMichael Fedkenheuer0Yafang Shang1Seolkyoung Jung2Kevin Fedkenheuer3Solji Park4Davide Mazza5Robin Sebastian6Hiroyuki Nagashima7Dali Zong8Hua Tan9Sushil Kumar Jaiswal10Haiqing Fu11Anthony Cruz12Supriya V. Vartak13Jan Wisniewski14Vittorio Sartorelli15John J. O’Shea16Laura Elnitski17Andre Nussenzweig18Mirit I. Aladjem19Fei-Long Meng20Rafael Casellas21Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthKey Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of SciencesMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthTranslational and Functional Analysis Branch, National Human Genome Research Institute, National Institutes of HealthMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthExperimental Imaging Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIHMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthLaboratory of Genome Integrity, National Cancer Institute NIHTranslational and Functional Analysis Branch, National Human Genome Research Institute, National Institutes of HealthTranslational and Functional Analysis Branch, National Human Genome Research Institute, National Institutes of HealthDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIHTranslational Genetics and Genomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthEIB Microscopy and Digital Imaging Facility, National Cancer Institute NIHLaboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthMolecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthTranslational and Functional Analysis Branch, National Human Genome Research Institute, National Institutes of HealthLaboratory of Genome Integrity, National Cancer Institute NIHDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIHKey Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of SciencesDepartment of Hematopoietic Biology & Malignancy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer CenterAbstract 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.https://doi.org/10.1038/s41467-025-56086-4 |
| spellingShingle | Michael Fedkenheuer Yafang Shang Seolkyoung Jung Kevin Fedkenheuer Solji Park Davide Mazza Robin Sebastian Hiroyuki Nagashima Dali Zong Hua Tan Sushil Kumar Jaiswal Haiqing Fu Anthony Cruz Supriya V. Vartak Jan Wisniewski Vittorio Sartorelli John J. O’Shea Laura Elnitski Andre Nussenzweig Mirit I. Aladjem Fei-Long Meng Rafael Casellas A dual role of Cohesin in DNA DSB repair Nature Communications |
| title | A dual role of Cohesin in DNA DSB repair |
| title_full | A dual role of Cohesin in DNA DSB repair |
| title_fullStr | A dual role of Cohesin in DNA DSB repair |
| title_full_unstemmed | A dual role of Cohesin in DNA DSB repair |
| title_short | A dual role of Cohesin in DNA DSB repair |
| title_sort | dual role of cohesin in dna dsb repair |
| url | https://doi.org/10.1038/s41467-025-56086-4 |
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