title: A homologue of the Rad18 postreplication repair gene is required for DNA damage responses throughout the fission yeast cell cycle.
abstract: Cells activate DNA repair pathways and cell cycle checkpoints when they suffer damage to their genome. They also activate tolerance pathways that facilitate survival. In Escherichia coli, a mechanism known as postreplication repair (PRR) is used to bypass lesions that would otherwise present a physical block to DNA polymerase. PRR has also been proposed to occur in eukaryotic cells, although the partitioning of DNA synthesis to a discrete S-phase would suggest that it is only operative within a defined period of the cell cycle. Eukaryotic PRR has been most extensively studied in the budding yeast Saccharomyces cerevisiae. Two important genes for components of this repair pathway are RAD6, which encodes an ubiquitin-conjugating enzyme, and RAD18, which encodes a RING-finger protein and forms a heterodimer with Rad6p. Rad18p can also bind to DNA. We report here the identification of the Schizosaccharomyces pombe homologue of RAD18, which we have denoted rhp18. rhp18 mutants are hypersensitive to DNA-damaging agents, but show this hypersensitivity throughout the cell cycle. rhp18 mutants are characterised by a longer than usual DNA damage checkpoint arrest that is required for their residual viability following irradiation. Genetic analyses show that rhp18 controls a unique DNA damage repair/tolerance pathway that extends beyond the requirement to tolerate damage during S-phase, suggesting a broader definition of the function of this eukaryotic PRR protein.
authors.affiliation: Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.
authors.forename: H M
authors.initials: HM
authors.lastname: Verkade
authors.forename: T
authors.initials: T
authors.lastname: Teli
authors.forename: L V
authors.initials: LV
authors.lastname: Laursen
authors.forename: J M
authors.initials: JM
authors.lastname: Murray
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
mesh_terms: D000595:Amino Acid Sequence; D002453:Cell Cycle; D003001:Cloning, Molecular; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004261:DNA Replication / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics* / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014466:Ultraviolet Rays; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C085979:RAD16 protein, S pombe; C063607:RAD18 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins