Cairo Gisela, Greiwe Cora, Jung Gyu Ik, Blengini Cecilia, Schindler Karen, Lacefield Soni
Indiana University, Department of Biology, Bloomington, IN USA.
Geisel School of Medicine at Dartmouth, Department of Biochemistry and Cell Biology, Hanover, NH USA.
bioRxiv. 2023 Feb 5:2023.02.05.527197. doi: 10.1101/2023.02.05.527197.
Proper chromosome segregation depends on 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 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双定向动粒-微管附着的建立，这通常需要多轮的释放和重新附着。极光激酶B和C使动粒蛋白磷酸化，以释放无张力的附着。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中后期起始时间以及动粒-微管附着的校正。我们发现，由Bub1/Bub3途径定位的蛋白池以不同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蛋白磷酸酶1在动粒定位，使其去磷酸化Cdc20从而导致后期过早开始。对于错误校正，Bub1/Bub3和COMA途径在减数分裂中各自发挥重要作用，但在有丝分裂中具有补偿作用。最后，我们发现Haspin和Bub1/3途径共同作用以确保小鼠卵子发生过程中的错误校正。我们的结果表明，每个招募途径在空间上定位不同的动粒定位的极光激酶B/C蛋白池，它们在减数分裂和有丝分裂之间发挥不同的作用。
