Abstract
The level of Sirt2 protein is reduced in oocytes from aged mice, while exogenous expression of Sirt2 could ameliorate the maternal age-associated meiotic defects. To date, the underlying mechanism remains unclear. Here, we confirmed that specific depletion of Sirt2 disrupts maturational progression and spindle/chromosome organization in mouse oocytes, with compromised kinetochore-microtubule attachments. Candidate screening revealed that acetylation state of lysine 243 on BubR1 (BubR1-K243, an integral part of the spindle assembly checkpoint complex) functions during oocyte meiosis, and acetylation-mimetic mutant BubR1-K243Q results in the very similar phenotypes as Sirt2-knockdown oocytes. Furthermore, we found that nonacetylatable-mimetic mutant BubR1-K243R partly prevents the meiotic deficits in oocytes depleted of Sirt2. Importantly, BubR1-K243R overexpression in oocytes derived from aged mice markedly suppresses spindle/chromosome anomalies and thereupon lowers the incidence of aneuploid eggs. In sum, our data suggest that Sirt2-dependent BubR1 deacetylation involves in the regulation of meiotic apparatus in normal oocytes and mediates the effects of advanced maternal age on oocyte quality.