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

Vasso Makrantoni, Adam Ciesiolka, Conor Lawless, Josefin Fernius, Adele L. Marston, David Lydall, Michael J. R. Stark (Lead / Corresponding author)

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3 Citations (Scopus)
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Abstract

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 (NMD) 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 bi-orientation. 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.

Original languageEnglish
Pages (from-to)3203-3215
Number of pages13
JournalG3 : Genes, Genomes, Genetics
Volume7
Issue number9
Early online date28 Jul 2017
DOIs
Publication statusPublished - 7 Sep 2017

Keywords

  • Bir1
  • Chromosome bi - orientation
  • Kinetochore
  • Iml3 - Chl4 complex
  • Yeast

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