Shu complex SWS1-SWSAP1 promotes early steps in mouse meiotic recombination
Abreu, Carla M. (Memorial Sloan Kettering Cancer Center)
Prakash, Rohit (Memorial Sloan Kettering Cancer Center)
Romanienko, Peter J. (Rutgers-Cancer Institute of New Jersey)
Roig, Ignasi (Ignasi) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Keeney, Scott (Memorial Sloan Kettering Cancer Center)
Jasin, Maria (Memorial Sloan Kettering Cancer Center)
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia

Date:	2018
Abstract:	The DNA-damage repair pathway homologous recombination (HR) requires factors that promote the activity of strand-exchange protein RAD51 and its meiosis-specific homolog DMC1. Here we show that the Shu complex SWS1-SWSAP1, a candidate for one such HR regulator, is dispensable for mouse viability but essential for male and female fertility, promoting the assembly of RAD51 and DMC1 on early meiotic HR intermediates. Only a fraction of mutant meiocytes progress to form crossovers, which are crucial for chromosome segregation, demonstrating crossover homeostasis. Remarkably, loss of the DNA damage checkpoint kinase CHK2 rescues fertility in females without rescuing crossover numbers. Concomitant loss of the BRCA2 C terminus aggravates the meiotic defects in Swsap1 mutant spermatocytes, suggesting an overlapping role with the Shu complex during meiotic HR. These results demonstrate an essential role for SWS1-SWSAP1 in meiotic progression and emphasize the complex interplay of factors that ensure recombinase function.
Grants:	Ministerio de Economía y Competitividad BFU2016-80370-P
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Animals ; Base sequence ; BRCA2 protein ; Cell cycle proteins ; Checkpoint kinase 2 ; Chromosome pairing ; Crossing over, genetic ; DNA ; Female ; Infertility ; Male ; Meiosis ; Mice, Inbred C57BL ; Mice, Mutant strains ; Mutation ; Nuclear proteins ; Rad51 recombinase ; Recombination, Genetic ; Spermatozoa
Published in:	Nature communications, Vol. 9 (2018) , art. 3961, ISSN 2041-1723

DOI: 10.1038/s41467-018-06384-x
PMID: 30305635

13 p, 6.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles