PDF(Pubmed)
Abstract：
SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.
摘要：
SETDB2是准确染色体分离所需的H3K9组蛋白甲基转移酶。据报道，其H3K9组蛋白甲基转移酶活性在中期与染色体有关。这里,我们确认SETDB2是有丝分裂和准确染色体分离所必需的。然而,这些功能与其组蛋白甲基转移酶活性无关。进一步分析表明，SETDB2可以与BUBR1相互作用，并且是CDC20与BUBR1和APC/C复合物结合以及CYCLINB1降解所必需的。SETDB2调节CDC20与BUBR1或APC/C复合物结合的能力，细胞周期蛋白B1的稳定性也独立于其组蛋白甲基转移酶的活性。这些结果表明，SETDB2与BUBR1相互作用以促进CDC20与BUBR1和APC3的结合，然后降解CYCLINB1以确保准确的染色体分离和有丝分裂，独立于其组蛋白甲基转移酶活性。
