title: A role for DNA primase in coupling DNA replication to DNA damage response.
abstract: The temperature-sensitive yeast DNA primase mutant pri1-M4 fails to execute an early step of DNA replication and exhibits a dominant, allele-specific sensitivity to DNA-damaging agents. pri1-M4 is defective in slowing down the rate of S phase progression and partially delaying the G1-S transition in response to DNA damage. Conversely, the G2 DNA damage response and the S-M checkpoint coupling completion of DNA replication to mitosis are unaffected. The signal transduction pathway leading to Rad53p phosphorylation induced by DNA damage is proficient in pri1-M4, and cell cycle delay caused by Rad53p overexpression is counteracted by the pri1-M4 mutation. Altogether, our results suggest that DNA primase plays an essential role in a subset of the Rad53p-dependent checkpoint pathways controlling cell cycle progression in response to DNA damage.
authors.affiliation: Dipartimento di Genetica e di Biologia dei Microrganismi, Università degli Studi di Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Marini
authors.forename: A
authors.initials: A
authors.lastname: Pellicioli
authors.forename: V
authors.initials: V
authors.lastname: Paciotti
authors.forename: G
authors.initials: G
authors.lastname: Lucchini
authors.forename: P
authors.initials: P
authors.lastname: Plevani
authors.forename: D F
authors.initials: DF
authors.lastname: Stern
authors.forename: M
authors.initials: M
authors.lastname: Foiani
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage / Q000235:genetics*; D019915:DNA Primase; D004261:DNA Replication / Q000235:genetics*; D004795:Enzyme Stability / Q000235:genetics; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D007399:Interphase / Q000235:genetics; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008938:Mitosis / Q000235:genetics; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012316:RNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D008741:Methyl Methanesulfonate; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases