title: RRM3 regulates epigenetic conversions in Saccharomyces cerevisiae in conjunction with Chromatin Assembly Factor I.
abstract: Chromatin structures are transmitted to daughter cells through a complex system of nucleosome disassembly and re-assembly at the advancing replication forks. However, the role of replication pausing in the transmission and perturbation of chromatin structures has not been addressed. RRM3 encodes a DNA helicase, which facilitates replication at sites covered with non-histone protein complexes (tRNA genes, active gene promoters, telomeres) in Saccharomyces cerevisiae. In this report we show that the deletion of RRM3 reduces the frequency of epigenetic conversions in the subtelomeric regions of the chromosomes. This phenotype is strongly dependent on 2 histone chaperones, CAF-I and ASF1, which are involved in the reassembly of nucleosomes behind replication forks, but not on the histone chaperone HIR1. We also show that the deletion of RRM3 increases the spontaneous mutation rates in conjunction with CAF-I and ASF1, but not HIR1. Finally, we demonstrate that Rrm3p and CAF-I compete for the binding to the DNA replication clamp PCNA (Proliferating Cell Nuclear Antigen). We propose that the stalling of DNA replication predisposes to epigenetic conversions and that RRM3 and CAF-I play key roles in this process.
authors.affiliation: a Department of Molecular and Cellular Biology , University of Guelph , Ontario , Canada.
authors.forename: Brandon
authors.initials: B
authors.lastname: Wyse
authors.affiliation: a Department of Molecular and Cellular Biology , University of Guelph , Ontario , Canada.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Oshidari
authors.affiliation: a Department of Molecular and Cellular Biology , University of Guelph , Ontario , Canada.
authors.forename: Hollie
authors.initials: H
authors.lastname: Rowlands
authors.affiliation: a Department of Molecular and Cellular Biology , University of Guelph , Ontario , Canada.
authors.forename: Sanna
authors.initials: S
authors.lastname: Abbasi
authors.affiliation: a Department of Molecular and Cellular Biology , University of Guelph , Ontario , Canada.
authors.forename: Krassimir
authors.initials: K
authors.lastname: Yankulov
mesh_terms: D001667:Binding, Competitive; D056504:Chromatin Assembly Factor-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D056504:Chromatin Assembly Factor-1; D018809:Proliferating Cell Nuclear Antigen; C533589:RLF2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C459081:Rrm3 protein, S cerevisiae; D004265:DNA Helicases
keywords: CAF-I; RRM3; chromatin assembly; epigenetic conversions; replication fork