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Non-enzymatic roles of human RAD51 at stalled replication forks

Author

Listed:
  • Jennifer M. Mason

    (University of Chicago
    Clemson University
    Clemson University)

  • Yuen-Ling Chan

    (University of Chicago)

  • Ralph W. Weichselbaum

    (University of Chicago)

  • Douglas K. Bishop

    (University of Chicago
    University of Chicago)

Abstract

The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not D-loop activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. Here, we find that cells lacking RAD51’s enzymatic activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly, we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication fork regression, supporting a model in which fork regression depends on a non-enzymatic function of RAD51. We also show RAD51 promotes replication restart by both strand exchange-dependent and strand exchange-independent mechanisms.

Suggested Citation

  • Jennifer M. Mason & Yuen-Ling Chan & Ralph W. Weichselbaum & Douglas K. Bishop, 2019. "Non-enzymatic roles of human RAD51 at stalled replication forks," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12297-0
    DOI: 10.1038/s41467-019-12297-0
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    Cited by:

    1. Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Akbar Zainu & Pauline Dupaigne & Soumya Bouchouika & Julien Cau & Julie A. J. Clément & Pauline Auffret & Virginie Ropars & Jean-Baptiste Charbonnier & Bernard Massy & Raphael Mercier & Rajeev Kumar &, 2024. "FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Junyeop Lee & Keewon Sung & So Young Joo & Jun-Hyeon Jeong & Seong Keun Kim & Hyunsook Lee, 2022. "Dynamic interaction of BRCA2 with telomeric G-quadruplexes underlies telomere replication homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Kai-Hang Lei & Han-Lin Yang & Hao-Yen Chang & Hsin-Yi Yeh & Dinh Duc Nguyen & Tzu-Yu Lee & Xinxing Lyu & Megan Chastain & Weihang Chai & Hung-Wen Li & Peter Chi, 2021. "Crosstalk between CST and RPA regulates RAD51 activity during replication stress," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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