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A dual role of Cohesin in DNA DSB repair

Author

Listed:
  • Michael Fedkenheuer

    (National Institutes of Health)

  • Yafang Shang

    (University of Chinese Academy of Sciences)

  • Seolkyoung Jung

    (National Institutes of Health)

  • Kevin Fedkenheuer

    (National Institutes of Health)

  • Solji Park

    (National Institutes of Health)

  • Davide Mazza

    (Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute)

  • Robin Sebastian

    (NIH)

  • Hiroyuki Nagashima

    (National Institutes of Health)

  • Dali Zong

    (National Cancer Institute NIH)

  • Hua Tan

    (National Institutes of Health)

  • Sushil Kumar Jaiswal

    (National Institutes of Health)

  • Haiqing Fu

    (NIH)

  • Anthony Cruz

    (National Institutes of Health)

  • Supriya V. Vartak

    (National Institutes of Health)

  • Jan Wisniewski

    (National Cancer Institute NIH)

  • Vittorio Sartorelli

    (National Institutes of Health)

  • John J. O’Shea

    (National Institutes of Health)

  • Laura Elnitski

    (National Institutes of Health)

  • Andre Nussenzweig

    (National Cancer Institute NIH)

  • Mirit I. Aladjem

    (NIH)

  • Fei-Long Meng

    (University of Chinese Academy of Sciences)

  • Rafael Casellas

    (The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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 & , 2025. "A dual role of Cohesin in DNA DSB repair," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56086-4
    DOI: 10.1038/s41467-025-56086-4
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    References listed on IDEAS

    as
    1. Patrick L. Collins & Caitlin Purman & Sofia I. Porter & Vincent Nganga & Ankita Saini & Katharina E. Hayer & Greer L. Gurewitz & Barry P. Sleckman & Jeffrey J. Bednarski & Craig H. Bassing & Eugene M., 2020. "DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    2. Coline Arnould & Vincent Rocher & Florian Saur & Aldo S. Bader & Fernando Muzzopappa & Sarah Collins & Emma Lesage & Benjamin Bozec & Nadine Puget & Thomas Clouaire & Thomas Mangeat & Raphael Mourad &, 2023. "Author Correction: Chromatin compartmentalization regulates the response to DNA damage," Nature, Nature, vol. 624(7990), pages 1-1, December.
    3. Andrea M. Kaminski & Percy P. Tumbale & Matthew J. Schellenberg & R. Scott Williams & Jason G. Williams & Thomas A. Kunkel & Lars C. Pedersen & Katarzyna Bebenek, 2018. "Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Coline Arnould & Vincent Rocher & Anne-Laure Finoux & Thomas Clouaire & Kevin Li & Felix Zhou & Pierre Caron & Philippe. E. Mangeot & Emiliano P. Ricci & Raphaël Mourad & James E. Haber & Daan Noorder, 2021. "Loop extrusion as a mechanism for formation of DNA damage repair foci," Nature, Nature, vol. 590(7847), pages 660-665, February.
    5. Coline Arnould & Vincent Rocher & Florian Saur & Aldo S. Bader & Fernando Muzzopappa & Sarah Collins & Emma Lesage & Benjamin Bozec & Nadine Puget & Thomas Clouaire & Thomas Mangeat & Raphael Mourad &, 2023. "Chromatin compartmentalization regulates the response to DNA damage," Nature, Nature, vol. 623(7985), pages 183-192, November.
    6. Jacob T. Sanders & Trevor F. Freeman & Yang Xu & Rosela Golloshi & Mary A. Stallard & Ashtyn M. Hill & Rebeca San Martin & Adayabalam S. Balajee & Rachel Patton McCord, 2020. "Radiation-induced DNA damage and repair effects on 3D genome organization," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    7. Christian H. Haering & Ana-Maria Farcas & Prakash Arumugam & Jean Metson & Kim Nasmyth, 2008. "The cohesin ring concatenates sister DNA molecules," Nature, Nature, vol. 454(7202), pages 297-301, July.
    8. Stephen P. Jackson & Jiri Bartek, 2009. "The DNA-damage response in human biology and disease," Nature, Nature, vol. 461(7267), pages 1071-1078, October.
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