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A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis
Centre for Gene Regulation and Expression, University of Dundee, UK.
Institute for Cell and Molecular Biosciences, Newcastle University, UK.
Institute for Cell and Molecular Biosciences, Newcastle University, UK.
Wellcome Trust Centre for Cell Biology, University of Edinburgh, UK.
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2017 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 7, no 9, p. 3203-3215Article in journal (Refereed) Published
Abstract [en]

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 Delta or chl4 Delta 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.

Place, publisher, year, edition, pages
GENETICS SOCIETY AMERICA , 2017. Vol. 7, no 9, p. 3203-3215
Keywords [en]
Bir1; Chromosome biorientation; Kinetochore; Iml3-Chl4 complex; yeast
National Category
Genetics
Identifiers
URN: urn:nbn:se:liu:diva-141122DOI: 10.1534/g3.117.300089ISI: 000409529500030PubMedID: 28754723OAI: oai:DiVA.org:liu-141122DiVA, id: diva2:1144760
Note

Funding Agencies|Biotechnology and Biological Sciences Research Council [BB/G003440/1]; Wellcome Trust [090903, 107827, 092076, 203149, 083524/Z/07/Z]; VIP award [092416/Z/10/Z]

Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2018-08-16

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