title: Proper functioning of the GINS complex is important for the fidelity of DNA replication in yeast.
abstract: The role of replicative DNA polymerases in ensuring genome stability is intensively studied, but the role of other components of the replisome is still not fully understood. One of such component is the GINS complex (comprising the Psf1, Psf2, Psf3 and Sld5 subunits), which participates in both initiation and elongation of DNA replication. Until now, the understanding of the physiological role of GINS mostly originated from biochemical studies. In this article, we present genetic evidence for an essential role of GINS in the maintenance of replication fidelity in Saccharomyces cerevisiae. In our studies we employed the psf1-1 allele (Takayama et al., 2003) and a novel psf1-100 allele isolated in our laboratory. Analysis of the levels and specificity of mutations in the psf1 strains indicates that the destabilization of the GINS complex or its impaired interaction with DNA polymerase epsilon increases the level of spontaneous mutagenesis and the participation of the error-prone DNA polymerase zeta. Additionally, a synergistic mutator effect was found for the defects in Psf1p and in the proofreading activity of Pol epsilon, suggesting that proper functioning of GINS is crucial for facilitating error-free processing of terminal mismatches created by Pol epsilon.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Grabowska
authors.forename: Urszula
authors.initials: U
authors.lastname: Wronska
authors.forename: Milena
authors.initials: M
authors.lastname: Denkiewicz
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jaszczur
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Respondek
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Alabrudzinska
authors.forename: Catherine
authors.initials: C
authors.lastname: Suski
authors.forename: Karolina
authors.initials: K
authors.lastname: Makiela-Dzbenska
authors.forename: Piotr
authors.initials: P
authors.lastname: Jonczyk
authors.forename: Iwona J
authors.initials: IJ
authors.lastname: Fijalkowska
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D050505:Mutant Proteins; D009687:Nuclear Proteins; C439312:PFS1 protein, S cerevisiae; C513448:PSF3 protein, S cerevisiae; C404156:Pfs2 protein, S cerevisiae; C474736:SLD5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors