title: A role for Chd1 and Set2 in negatively regulating DNA replication in Saccharomyces cerevisiae.
abstract: Chromatin-modifying factors regulate both transcription and DNA replication. The yFACT chromatin-reorganizing complex is involved in both processes, and the sensitivity of some yFACT mutants to the replication inhibitor hydroxyurea (HU) is one indication of a replication role. This HU sensitivity can be suppressed by disruptions of the SET2 or CHD1 genes, encoding a histone H3(K36) methyltransferase and a chromatin remodeling factor, respectively. The additive effect of set2 and chd1 mutations in suppressing the HU sensitivity of yFACT mutants suggests that these two factors function in separate pathways. The HU suppression is not an indirect effect of altered regulation of ribonucleotide reductase induced by HU. set2 and chd1 mutations also suppress the HU sensitivity of mutations in other genes involved in DNA replication, including CDC2, CTF4, ORC2, and MEC1. Additionally, a chd1 mutation can suppress the lethality normally caused by disruption of either MEC1 or RAD53 DNA damage checkpoint genes, as well as the lethality seen when a mec1 sml1 mutant is exposed to low levels of HU. The pob3 defect in S-phase progression is suppressed by set2 or chd1 mutations, suggesting that Set2 and Chd1 have specific roles in negatively regulating DNA replication.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84112, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Biswas
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahata
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Rinku
authors.initials: R
authors.lastname: Dutta-Biswas
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Yu
authors.forename: Tim
authors.initials: T
authors.lastname: Formosa
authors.forename: David J
authors.initials: DJ
authors.lastname: Stillman
mesh_terms: D002843:Chromatin / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D006918:Hydroxyurea / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C489847:CHD1 protein, S cerevisiae; D002843:Chromatin; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D012262:Ribonucleoside Diphosphate Reductase; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; D006918:Hydroxyurea