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bioRxiv · 10.1101/238196

Shu complex SWS1-SWSAP1 is required for mouse meiotic recombination in concert with the BRCA2 C terminus

Abreu, C. M.·Prakash, R.·Romanienko, P. J.·Roig, I.·Keeney, S.·Jasin, M.
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Abstract

Homology recognition and DNA-strand invasion ensure faithful homolog pairing and segregation during the first meiotic division1. RAD51 and DMC1 recombinases catalyze these steps2, with BRCA2 promoting their assembly into nuclear foci3. The recently identified human SWS1-SWSAP1 complex, related to the Shu complex in yeast, promotes RAD51 focus formation in cell lines4,5. We show here that mouse SWS1-SWSAP1 is critical for meiotic homologous recombination (HR) by promoting the assembly of RAD51 and DMC1 on early recombination intermediates. Absence of the complex perturbs meiotic progression in males and females and both sexes are sterile, although a fraction of meiocytes form crossovers. Remarkably, loss of the DNA damage checkpoint kinase CHK2 rescues fertility specifically in females without rescuing crossover numbers. Unlike the Shu complex, the BRCA2 C terminus (known to be required for RAD51 stabilization6,7) is dispensible for RAD51 and DMC1 focus formation. However, concomitant loss of the BRCA2 C terminus aggravates the meiotic defects in Shu mutant spermatocytes. These results point to a complex interplay of factors that ensure recombinase function and hence meiotic progression in the mouse.

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Abreu, C. M., Prakash, R., Romanienko, P. J., Roig, I., Keeney, S., Jasin, M.. 2017-12-22. Shu complex SWS1-SWSAP1 is required for mouse meiotic recombination in concert with the BRCA2 C terminus. https://doi.org/10.1101/238196

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