A Functional Link Between Bir1 and the Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis.

The chromosomal passenger complex (CPC) is a key regulator of eukaryotic cell division, consisting of the protein kinase Aurora B/Ipl1 in association with its activator (INCENP/Sli15) and two additional proteins (Survivin/Bir1 and Borealin/Nbl1). Here, we report a genome-wide genetic interaction screen in using the mutant, identifying through quantitative fitness analysis deletion mutations that act as enhancers and suppressors. Gene knockouts affecting the Ctf19 kinetochore complex were identified as the strongest enhancers of , while mutations affecting the large ribosomal subunit or the mRNA nonsense-mediated decay pathway caused strong phenotypic suppression. Thus, cells lacking a functional Ctf19 complex become highly dependent on Bir1 function and vice versa. The negative genetic interaction profiles of and the cohesin mutant showed considerable overlap, underlining the strong functional connection between sister chromatid cohesion and chromosome biorientation. Loss of some Ctf19 components, such as Iml3 or Chl4, impacted differentially on compared with mutations affecting other CPC components: despite the synthetic lethality shown by either ∆ or ∆ in combination with , neither gene knockout showed any genetic interaction with either or Our data therefore imply a specific functional connection between the Ctf19 complex and Bir1 that is not shared with Ipl1.