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

Abstract : 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.
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https://hal-amu.archives-ouvertes.fr/hal-03438617
Contributor : Mauro Modesti Connect in order to contact the contributor
Submitted on : Sunday, November 21, 2021 - 7:42:21 PM
Last modification on : Monday, November 22, 2021 - 3:40:29 AM

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Mauro Modesti, Rohit Prakash, Thomas Sandoval, Florian Morati, Jennifer Zagelbaum, et al.. Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex. Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-24205-6⟩. ⟨hal-03438617⟩

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