Distinct Aurora B pools at the inner centromere and kinetochore have different contributions to meiotic and mitotic chromosome segregation

Abstract

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 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.

Low tension recruits the yeast Aurora B protein Ipl1 to centromeres in metaphase

“…Previous studies have revealed that there are several mechanisms that can recruit CPC-Aurora B or -Ipl1 to centromeres, kinetochores and mitotic spindles ( Bonner et al, 2019 ; Broad and DeLuca, 2020 ; Broad et al, 2020 ; Cairo et al, 2023 ; Campbell and Desai, 2013 ; Fischbock-Halwachs et al, 2019 ; Garcia-Rodriguez et al, 2019 ; Haase et al, 2017 ; Hadders et al, 2020 ; Liang et al, 2020 ; Marsoner et al, 2022 ). In our experiments, we did not attempt to distinguish between these different localization patterns of Ipl1, and instead we defined recruitment as concentrated localization between the SPBs.…”

“…Bub1 kinase phosphorylates H2A threonine 120 (H2A Serine 121 in yeast) at kinetochore-proximal centromeres, which recruits shugoshin (Sgo1), providing a binding site for the borealin CPC component ( Kawashima et al, 2007 ; Peplowska et al, 2014 ; Tsukahara et al, 2010 ; Yamagishi et al, 2010 ). In addition to these interactions, other studies have shown CPC–Aurora B or Ipl1 recruitment to inner kinetochores via the COMA complex ( Cairo et al, 2023 ; Fischbock-Halwachs et al, 2019 ; Garcia-Rodriguez et al, 2019 ), and even to spindle microtubules ( Campbell and Desai, 2013 ). Despite the detailed information about these recruitment mechanisms, the biological contexts that induce Aurora B recruitment to centromeres remain less well understood.…”