Translator Disclaimer
1 October 2008 BRCA1 Is Required for Meiotic Spindle Assembly and Spindle Assembly Checkpoint Activation in Mouse Oocytes
Bo Xiong, Sen Li, Jun-Shu Ai, Shen Yin, Ying-Chun OuYang, Shao-Chen Sun, Da-Yuan Chen, Qing-Yuan Sun
Author Affiliations +
Abstract

BRCA1 as a tumor suppressor has been widely investigated in mitosis, but its functions in meiosis are unclear. In the present study, we examined the expression, localization, and function of BRCA1 during mouse oocyte meiotic maturation. We found that expression level of BRCA1 was increased progressively from germinal vesicle to metaphase I stage, and then remained stable until metaphase II stage. Immunofluorescent analysis showed that BRCA1 was localized to the spindle poles at metaphase I and metaphase II stages, colocalizing with centrosomal protein gamma-tubulin. Taxol treatment resulted in the presence of BRCA1 onto the spindle microtubule fibers, whereas nocodazole treatment induced the localization of BRCA1 onto the chromosomes. Depletion of BRCA1 by both antibody injection and siRNA injection caused severely impaired spindles and misaligned chromosomes. Furthermore, BRCA1-depleted oocytes could not arrest at the metaphase I in the presence of low-dose nocodazole, suggesting that the spindle checkpoint is defective. Also, in BRCA1-depleted oocytes, gamma-tubulin dissociated from spindle poles and MAD2L1 failed to rebind to the kinetochores when exposed to nocodazole at metaphase I stage. Collectively, these data indicate that BRCA1 regulates not only meiotic spindle assembly, but also spindle assembly checkpoint, implying a link between BRCA1 deficiency and aneuploid embryos.

Bo Xiong, Sen Li, Jun-Shu Ai, Shen Yin, Ying-Chun OuYang, Shao-Chen Sun, Da-Yuan Chen, and Qing-Yuan Sun "BRCA1 Is Required for Meiotic Spindle Assembly and Spindle Assembly Checkpoint Activation in Mouse Oocytes," Biology of Reproduction 79(4), 718-726, (1 October 2008). https://doi.org/10.1095/biolreprod.108.069641
Received: 2 April 2008; Accepted: 1 June 2008; Published: 1 October 2008
JOURNAL ARTICLE
9 PAGES


Share
SHARE
KEYWORDS
aneuploid embryo
BRCA1
meiosis
mouse oocyte
spindle assembly
spindle assembly checkpoint
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top