ALBERT

Description: 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 Saccharomyces cerevisiae using the bir1 -17 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 bir1 -17 , 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 bir1 -17 and the cohesin mutant mcd1 -1 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 bir1 -17 compared with mutations affecting other CPC components: despite the synthetic lethality shown by either iml3 or chl4 in combination with bir1 -17 , neither gene knockout showed any genetic interaction with either ipl1 -321 or sli15 -3 . Our data therefore imply a specific functional connection between the Ctf19 complex and Bir1 that is not shared with Ipl1 .