A Genome-Wide Screen Reveals a Role for the HIR Histone Chaperone Complex in Preventing Mislocalization of Budding Yeast CENP-A

Genetics
Sultan Ciftci-YilmazMunira A Basrai

Abstract

Centromeric localization of the evolutionarily conserved centromere-specific histone H3 variant CENP-A (Cse4 in yeast) is essential for faithful chromosome segregation. Overexpression and mislocalization of CENP-A lead to chromosome segregation defects in yeast, flies, and human cells. Overexpression of CENP-A has been observed in human cancers; however, the molecular mechanisms preventing CENP-A mislocalization are not fully understood. Here, we used a genome-wide synthetic genetic array (SGA) to identify gene deletions that exhibit synthetic dosage lethality (SDL) when Cse4 is overexpressed. Deletion for genes encoding the replication-independent histone chaperone HIR complex (HIR1, HIR2, HIR3, HPC2) and a Cse4-specific E3 ubiquitin ligase, PSH1, showed highest SDL. We defined a role for Hir2 in proteolysis of Cse4 that prevents mislocalization of Cse4 to noncentromeric regions for genome stability. Hir2 interacts with Cse4 in vivo, and hir2∆ strains exhibit defects in Cse4 proteolysis and stabilization of chromatin-bound Cse4 Mislocalization of Cse4 to noncentromeric regions with a preferential enrichment at promoter regions was observed in hir2∆ strains. We determined that Hir2 facilitates the interaction of Cse4 with Psh1,...Continue Reading

References

Jan 1, 1991·Annual Review of Biochemistry·M A Osley
Nov 26, 1999·Gene·C Seoighe, K H Wolfe
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 7, 2004·Science·Amy Hin Yan TongCharles Boone
Jul 16, 2004·Molecular and Cellular Biology·Gerhard WielandPeter Hemmerich
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Jul 2, 2005·Biochimie·Akash GunjanAlain Verreault
Oct 7, 2005·Molecular Biology of the Cell·Kimberly A CollinsSue Biggins
Nov 24, 2005·Current Biology : CB·Erin M GreenPaul D Kaufman
Mar 3, 2006·Genome Research·James P KastenmayerMunira A Basrai
Jun 26, 2007·Molecular Genetics and Genomics : MGG·Prashant K MishraJohn Carbon
Nov 13, 2008·Nature Reviews. Genetics·Robin C Allshire, Gary H Karpen
Nov 6, 2009·Annual Review of Genetics·Marcin R Przewloka, David M Glover
Dec 17, 2009·Molecular Cancer·Angela AmatoAldo Di Leonardo
Jan 23, 2010·Science·Michael CostanzoCharles Boone
Oct 16, 2010·Methods in Enzymology·Anastasia BaryshnikovaCharles Boone
Nov 13, 2010·Molecular Cell·Geetha HewawasamJennifer L Gerton
Nov 16, 2010·Nature Methods·Anastasia BaryshnikovaChad L Myers
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Apr 22, 2011·Nature Reviews. Molecular Cell Biology·Jolien S Verdaasdonk, Kerry Bloom
Aug 30, 2011·Current Biology : CB·Olga Moreno-MorenoFernando Azorín
Dec 1, 2011·The Journal of Biological Chemistry·Andrea C SilvaMichael-Christopher Keogh
Dec 20, 2011·Current Opinion in Genetics & Development·Paul S MaddoxArshad Desai
Mar 1, 2012·Biochimica Et Biophysica Acta·John S ChoyMunira A Basrai
Mar 27, 2012·Trends in Genetics : TIG·Laura S Burrack, Judith Berman

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Citations

Feb 26, 2020·Genes·Julius Muellner, Kristina H Schmidt
Apr 17, 2020·G3 : Genes - Genomes - Genetics·Jessica R EisenstattMunira A Basrai
Aug 14, 2020·Genes·Ganesan Arunkumar, Daniël P Melters
Feb 24, 2021·The Journal of Cell Biology·Roshan L ShresthaMunira A Basrai
Aug 26, 2021·Molecular Biology of the Cell·Prashant K MishraMunira A Basrai

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