Department of Biology, Indiana University, Bloomington, IN 47405.
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
Mol Biol Cell. 2023 May 1;34(5):ar43. doi: 10.1091/mbc.E23-01-0014. Epub 2023 Mar 15.
Proper chromosome segregation depends on the establishment of bioriented kinetochore-microtubule attachments, which often requires multiple rounds of release and reattachment. Aurora B and C kinases phosphorylate kinetochore proteins to release tensionless attachments. Multiple pathways recruit Aurora B/C to the centromere and kinetochore. We studied how these pathways contribute to anaphase onset timing and correction of kinetochore-microtubule attachments in budding yeast meiosis and mitosis. We find that the pool localized by the Bub1/Bub3 pathway sets the normal duration of meiosis and mitosis, in differing ways. Our meiosis data suggests a model that disruption of this pathway leads to PP1 kinetochore localization, which dephosphorylates Cdc20 for premature anaphase onset. For error correction, the Bub1/Bub3 and COMA pathways are individually important in meiosis but compensatory in mitosis. Finally, we find that the haspin and Bub1/3 pathways function together to ensure error correction in mouse oogenesis. Our results suggest that each recruitment pathway localizes spatially distinct kinetochore-localized Aurora B/C pools that function differently between meiosis and mitosis.
正确的染色体分离依赖于建立对向的动粒微管连接,这通常需要多次释放和重新连接。极光激酶 B 和 C 使动粒蛋白磷酸化以释放无张力的连接。多种途径将极光激酶 B/C 招募到着丝粒和动粒。我们研究了这些途径如何影响芽殖酵母减数分裂和有丝分裂的后期起始时间和动粒微管连接的校正。我们发现,由 Bub1/Bub3 途径定位的池以不同的方式设定了减数分裂和有丝分裂的正常持续时间。我们的减数分裂数据表明,该途径的破坏会导致 PP1 动粒定位,从而使 Cdc20 去磷酸化,导致过早的后期起始。对于错误校正,Bub1/Bub3 和 COMA 途径在减数分裂中各自重要,但在有丝分裂中具有补偿作用。最后,我们发现 Haspin 和 Bub1/3 途径在确保小鼠卵母细胞减数分裂的错误校正中共同发挥作用。我们的结果表明,每个招募途径将空间上不同的动粒定位的极光激酶 B/C 池定位,这些池在减数分裂和有丝分裂中的作用不同。