title: Mutations in the Non-Catalytic Subunit Dpb2 of DNA Polymerase Epsilon Affect the Nrm1 Branch of the DNA Replication Checkpoint.
abstract: To preserve genome integrity, the S-phase checkpoint senses damaged DNA or nucleotide depletion and when necessary, arrests replication progression and delays cell division. Previous studies, based on two pol2 mutants have suggested the involvement of DNA polymerase epsilon (Pol ε) in sensing DNA replication accuracy in Saccharomyces cerevisiae. Here we have studied the involvement of Pol ε in sensing proper progression of DNA replication, using a mutant in DPB2, the gene coding for a non-catalytic subunit of Pol ε. Under genotoxic conditions, the dpb2-103 cells progress through S phase faster than wild-type cells. Moreover, the Nrm1-dependent branch of the checkpoint, which regulates the expression of many replication checkpoint genes, is impaired in dpb2-103 cells. Finally, deletion of DDC1 in the dpb2-103 mutant is lethal supporting a model of strand-specific activation of the replication checkpoint. This lethality is suppressed by NRM1 deletion. We postulate that improper activation of the Nrm1-branch may explain inefficient replication checkpoint activation in Pol ε mutants.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences Pawińskiego 5a, Warsaw, POLAND.
authors.forename: Michał
authors.identifier: 0000-0002-6571-6259
authors.initials: M
authors.lastname: Dmowski
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences Pawińskiego 5a, Warsaw, POLAND.
authors.forename: Justyna
authors.initials: J
authors.lastname: Rudzka
authors.affiliation: Braun Laboratories, California Institute of Technology, Pasadena, CA, United States of America.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Campbell
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences Pawińskiego 5a, Warsaw, POLAND.
authors.forename: Piotr
authors.initials: P
authors.lastname: Jonczyk
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences Pawińskiego 5a, Warsaw, POLAND.
authors.forename: Iwona J
authors.initials: IJ
authors.lastname: Fijałkowska
mesh_terms: D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C513403:Nrm1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C529202:Dpb2 protein, S cerevisiae; D004257:DNA Polymerase II