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

Lookup NU author(s): Adam Ciesiolka, Dr Conor LawlessORCiD, Emeritus Professor David Lydall

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2017 Makrantoni et al. 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 nonsensemediated 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 iml3Δ or chl4Δ 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.

Publication metadata

Author(s): Makrantoni V, Ciesiolka A, Lawless C, Fernius J, Marston A, Lydall D, Stark MJR

Publication type: Article

Publication status: Published

Journal: G3: Genes, Genomes, Genetics

Year: 2017

Volume: 7

Issue: 9

Pages: 3203-3215

Online publication date: 01/09/2017

Acceptance date: 25/07/2017

Date deposited: 10/01/2018

ISSN (print): 2160-1836

Publisher: Genetics Society of America

URL: https://doi.org/10.1534/g3.117.300089

DOI: 10.1534/g3.117.300089

PubMed id: 28754723

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