Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis.
The key step for faithful chromosome segregation during meiosis is kinetochore assembly. Defects in this process result in aneuploidy, leading to miscarriages, infertility and various birth defects. However, the roles of kinetochores in homologous chromosome segregation during meiosis are ill-defined. Here we found that Zwint-1 is required for homologous chromosome segregation during meiosis. Knockdown of Zwint-1 accelerated the first meiosis by abrogating the kinetochore recruitment of Mad2, leading to chromosome misalignment and a high incidence of aneuploidy. Although Zwint-1 knockdown did not affect Aurora C kinase activity, the meiotic defects following Zwint-1 knockdown were similar to those observed with ZM447439 treatment. Importantly, the chromosome misalignment following Aurora C kinase inhibition was not restored after removing the inhibitor in Zwint-1-knockdown oocytes, whereas the defect was rescued after the inhibitor washout in the control oocytes. These results suggest that Aurora C kinase-mediated correction of erroneous kinetochore-microtubule attachment is primarily regulated by Zwint-1. Our results provide the first evidence that Zwint-1 is required to correct erroneous kinetochore-microtubule attachment and regulate spindle checkpoint function during meiosis.
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Korea.
Dong
D
Woo Seo
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Korea.
Seung
S
Yeop You
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Korea.
Woo-Jae
WJ
Chung
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Dong-Hyung
DH
Cho
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Jae-Sung
JS
Kim
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Korea.
Jeong
J
Su Oh
D000782:Aneuploidy; D064108:Aurora Kinase C / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D018386:Kinetochores; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D009865:Oocytes / Q000254:growth & development
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C413695:ZWINT protein, human; D064108:Aurora Kinase C