SPIDR is required for homologous recombination during mammalian meiosis

• Published in: Nucleic acids research 2023-05, Vol.51 (8), p.3855-3868
• Main Authors: Huang, Tao, Wu, Xinyue, Wang, Shiyu, Bao, Ziyou, Wan, Yanling, Wang, Ziqi, Li, Mengjing, Yu, Xiaochen, Lv, Yue, Liu, Zhaojian, Chen, Xiangfeng, Chan, Wai-Yee, Gao, Fei, Lu, Gang, Chen, Zi-Jiang, Liu, Hongbin
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosome Pairing - genetics; DNA Repair; Homologous Recombination - genetics; Male; Mammals - metabolism; Meiosis - genetics; Mice; Mice, Knockout; Molecular Biology; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkad154

Abstract Meiotic recombinases RAD51 and DMC1 mediate strand exchange in the repair of DNA double-strand breaks (DSBs) by homologous recombination. This is a landmark event of meiosis that ensures genetic diversity in sexually reproducing organisms. However, the regulatory mechanism of DMC1/RAD51-ssDNA nucleoprotein filaments during homologous recombination in mammals has remained largely elusive. Here, we show that SPIDR (scaffold protein involved in DNA repair) regulates the assembly or stability of RAD51/DMC1 on ssDNA. Knockout of Spidr in male mice causes complete meiotic arrest, accompanied by defects in synapsis and crossover formation, which leads to male infertility. In females, loss of Spidr leads to subfertility; some Spidr−/− oocytes are able to complete meiosis. Notably, fertility is rescued partially by ablation of the DNA damage checkpoint kinase CHK2 in Spidr−/− females but not in males. Thus, our study identifies SPIDR as an essential meiotic recombination factor in homologous recombination in mammals.