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Publication : Overexpression of SETβ, a protein localizing to centromeres, causes precocious separation of chromatids during the first meiosis of mouse oocytes.

First Author  Qi ST Year  2013
Journal  J Cell Sci Volume  126
Issue  Pt 7 Pages  1595-603
PubMed ID  23444375 Mgi Jnum  J:200659
Mgi Id  MGI:5509000 Doi  10.1242/jcs.116541
Citation  Qi ST, et al. (2013) Overexpression of SETbeta, a protein localizing to centromeres, causes precocious separation of chromatids during the first meiosis of mouse oocytes. J Cell Sci 126(Pt 7):1595-603
abstractText  Chromosome segregation in mammalian oocyte meiosis is an error-prone process, and any mistake in this process may result in aneuploidy, which is the main cause of infertility, abortion and many genetic diseases. It is now well known that shugoshin and protein phosphatase 2A (PP2A) play important roles in the protection of centromeric cohesion during the first meiosis. PP2A can antagonize the phosphorylation of rec8, a member of the cohesin complex, at the centromeres and thus prevent cleavage of rec8 and so maintain the cohesion of chromatids. SETbeta is a protein that physically interacts with shugoshin and inhibits PP2A activity. We thus hypothesized that SETbeta might regulate cohesion protection and chromosome segregation during oocyte meiotic maturation. Here we report for the first time the expression, subcellular localization and functions of SETbeta during mouse oocyte meiosis. Immunoblotting analysis showed that the expression level of SETbeta was stable from the germinal vesicle stage to the MII stage of oocyte meiosis. Immunofluorescence analysis showed SETbeta accumulation in the nucleus at the germinal vesicle stage, whereas it was targeted mainly to the inner centromere area and faintly localized to the interchromatid axes from germinal vesicle breakdown to MI stages. At the MII stage, SETbeta still localized to the inner centromere area, but could relocalize to kinetochores in a process perhaps dependent on the tension on the centromeres. SETbeta partly colocalized with PP2A at the inner centromere area. Overexpression of SETbeta in mouse oocytes caused precocious separation of sister chromatids, but depletion of SETbeta by RNAi showed little effects on the meiotic maturation process. Taken together, our results suggest that SETbeta, even though it localizes to centromeres, might not be essential for chromosome separation during mouse oocyte meiotic maturation, although its forced overexpression causes premature chromatid separation.
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