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Profilin-1 regulates DNA replication forks in a context-dependent fashion by interacting with SNF2H and BOD1L

Author

Listed:
  • Cuige Zhu

    (Washington University School of Medicine)

  • Mari Iwase

    (Washington University School of Medicine)

  • Ziqian Li

    (Washington University School of Medicine
    Sun Yat-sen University)

  • Faliang Wang

    (Washington University School of Medicine)

  • Annabel Quinet

    (Washington University School of Medicine
    University of Paris and University of Paris-Saclay, INSERM, iRCM/IBFJ CEA)

  • Alessandro Vindigni

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Jieya Shao

    (Washington University School of Medicine
    Washington University School of Medicine)

Abstract

DNA replication forks are tightly controlled by a large protein network consisting of well-known core regulators and many accessory factors which remain functionally undefined. In this study, we report previously unknown nuclear functions of the actin-binding factor profilin-1 (PFN1) in DNA replication, which occur in a context-dependent fashion and require its binding to poly-L-proline (PLP)-containing proteins instead of actin. In unperturbed cells, PFN1 increases DNA replication initiation and accelerates fork progression by binding and stimulating the PLP-containing nucleosome remodeler SNF2H. Under replication stress, PFN1/SNF2H increases fork stalling and functionally collaborates with fork reversal enzymes to enable the over-resection of unprotected forks. In addition, PFN1 binds and functionally attenuates the PLP-containing fork protector BODL1 to increase the resection of a subset of stressed forks. Accordingly, raising nuclear PFN1 level decreases genome stability and cell survival during replication stress. Thus, PFN1 is a multi-functional regulator of DNA replication with exploitable anticancer potential.

Suggested Citation

  • Cuige Zhu & Mari Iwase & Ziqian Li & Faliang Wang & Annabel Quinet & Alessandro Vindigni & Jieya Shao, 2022. "Profilin-1 regulates DNA replication forks in a context-dependent fashion by interacting with SNF2H and BOD1L," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34310-9
    DOI: 10.1038/s41467-022-34310-9
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