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

   


Authors: Prakash, R.; Sandoval, T.; Morati, F.; Zagelbaum, J. A.; Lim, P. X.; White, T.; Taylor, B.; Wang, R.; Desclos, E. C. B.; Sullivan, M. R.; Rein, H. L.; Bernstein, K. A.; Krawczyk, P. M.; Gautier, J.; Modesti, M.; Vanoli, F.; Jasin, M.
Article Title: Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex
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. © 2021, The Author(s).
Keywords: mammalia
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-07-12
Start Page: 4255
Language: English
DOI: 10.1038/s41467-021-24205-6
PROVIDER: scopus
PMCID: PMC8275761
PUBMED: 34253720
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85110645062&doi=10.1038%2fs41467-021-24205-6&partnerID=40&md5=c1b8ecacaa673be43b22b7c118878538
Notes: Article -- Export Date: 2 August 2021 -- Source: Scopus
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MSK Authors
  1. Rohit Prakash
    14 Prakash
  2. Maria Jasin
    250 Jasin
  3. Fabio Vanoli
    22 Vanoli
  4. Raymond Qingwen Wang
    5 Wang
  5. Pei Xin Lim
    6 Lim
  6. Travis White
    5 White
  7. Thomas Michael Sandoval
    1 Sandoval
  8. Brett Taylor
    1 Taylor
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