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Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex

Author

Listed:
  • Rohit Prakash

    (Memorial Sloan Kettering Cancer Center)

  • Thomas Sandoval

    (Memorial Sloan Kettering Cancer Center)

  • Florian Morati

    (Cancer Research Center of Marseille, CNRS, Inserm, Institut Paoli-Calmettes, Aix-Marseille Université)

  • Jennifer A. Zagelbaum

    (Columbia University)

  • Pei-Xin Lim

    (Memorial Sloan Kettering Cancer Center)

  • Travis White

    (Memorial Sloan Kettering Cancer Center)

  • Brett Taylor

    (Memorial Sloan Kettering Cancer Center)

  • Raymond Wang

    (Memorial Sloan Kettering Cancer Center)

  • Emilie C. B. Desclos

    (Amsterdam University Medical Centers)

  • Meghan R. Sullivan

    (University of Pittsburgh School of Medicine)

  • Hayley L. Rein

    (University of Pittsburgh School of Medicine)

  • Kara A. Bernstein

    (University of Pittsburgh School of Medicine)

  • Przemek M. Krawczyk

    (Amsterdam University Medical Centers)

  • Jean Gautier

    (Columbia University)

  • Mauro Modesti

    (Cancer Research Center of Marseille, CNRS, Inserm, Institut Paoli-Calmettes, Aix-Marseille Université)

  • Fabio Vanoli

    (Memorial Sloan Kettering Cancer Center)

  • Maria Jasin

    (Memorial Sloan Kettering Cancer Center)

Abstract

Homology-directed repair (HDR), a critical DNA repair pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these different outcomes are often not well understood. Here we show that SWS1–SWSAP1-SPIDR controls distinct types of HDR. Despite their requirement for stable assembly of RAD51 recombinase at DNA damage sites, these proteins are not essential for intra-chromosomal HDR, providing insight into why patients and mice with mutations are viable. However, SWS1–SWSAP1-SPIDR is critical for inter-homolog HDR, the first mitotic factor identified specifically for this function. Furthermore, SWS1–SWSAP1-SPIDR drives the high level of sister-chromatid exchange, promotes long-range loss of heterozygosity often involved with cancer initiation, and impels the poor growth of BLM helicase-deficient cells. The relevance of these genetic interactions is evident as SWSAP1 loss prolongs Blm-mutant embryo survival, suggesting a possible druggable target for the treatment of Bloom syndrome.

Suggested Citation

  • Rohit Prakash & Thomas Sandoval & Florian Morati & Jennifer A. Zagelbaum & Pei-Xin Lim & Travis White & Brett Taylor & Raymond Wang & Emilie C. B. Desclos & Meghan R. Sullivan & Hayley L. Rein & Kara , 2021. "Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24205-6
    DOI: 10.1038/s41467-021-24205-6
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    References listed on IDEAS

    as
    1. Roger D. Johnson & Nan Liu & Maria Jasin, 1999. "Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination," Nature, Nature, vol. 401(6751), pages 397-399, September.
    2. Leonard Wu & Ian D. Hickson, 2003. "The Bloom's syndrome helicase suppresses crossing over during homologous recombination," Nature, Nature, vol. 426(6968), pages 870-874, December.
    3. Weiran Feng & Maria Jasin, 2017. "BRCA2 suppresses replication stress-induced mitotic and G1 abnormalities through homologous recombination," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    4. Edwige B Garcin & Stéphanie Gon & Meghan R Sullivan & Gregory J Brunette & Anne De Cian & Jean-Paul Concordet & Carine Giovannangeli & Wilhelm G Dirks & Sonja Eberth & Kara A Bernstein & Rohit Prakash, 2019. "Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells," PLOS Genetics, Public Library of Science, vol. 15(10), pages 1-29, October.
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    Cited by:

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    2. Masaru Ito & Asako Furukohri & Kenichiro Matsuzaki & Yurika Fujita & Atsushi Toyoda & Akira Shinohara, 2023. "FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Sarah R. Hengel & Katherine G. Oppenheimer & Chelsea M. Smith & Matthew A. Schaich & Hayley L. Rein & Julieta Martino & Kristie E. Darrah & Maggie Witham & Oluchi C. Ezekwenna & Kyle R. Burton & Benne, 2024. "The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Jessica D. Tischler & Hiroshi Tsuchida & Rosevalentine Bosire & Tommy T. Oda & Ana Park & Richard O. Adeyemi, 2024. "FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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