The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.
Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.
College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry Education, Huazhong Agricultural University, Wuhan, China.
Chun-Jie
CJ
Huang
Department of Gynecology and Obstetrics, Peking University Third University, Beijing, China.
Yi-Feng
YF
Yuan
College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry Education, Huazhong Agricultural University, Wuhan, China.
Di
D
Wu
College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry Education, Huazhong Agricultural University, Wuhan, China.
Faheem Ahmed
FA
Khan
College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry Education, Huazhong Agricultural University, Wuhan, China.
Xiao-Fei
XF
Jiao
College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry Education, Huazhong Agricultural University, Wuhan, China. lijunhuo@yahoo.com.
Li-Jun
LJ
Huo
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002503:Centromere / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics; D008540:Meiosis / Q000235:genetics*; D000090204:Mesothelin; D051379:Mice; D009865:Oocytes / Q000254:growth & development*; D059705:Polar Bodies / Q000166:cytology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000097869:Polo-Like Kinase 1
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D058851:GPI-Linked Proteins; D006657:Histones; D000090204:Mesothelin; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C500696:Cdca5 protein, mouse; C000715528:Msln protein, mouse; C496335:WAPL protein, mouse; C475961:gamma-H2AX protein, mouse
Chromosome separation; Cohesion; DNA damage; Oocyte meiosis; Sororin