title: PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.
abstract: Translesion DNA synthesis (TLS) involves PCNA mono-ubiquitination and TLS DNA polymerases (pols). Recent evidence has shown that the mono-ubiquitination is induced not only by DNA damage but also by other factors that induce stalling of the DNA replication fork. We studied the effect of spontaneous DNA replication errors on PCNA mono-ubiquitination and TLS induction. In the pol1L868F strain, which expressed an error-prone pol alpha, PCNA was spontaneously mono-ubiquitinated. Pol alpha L868F had a rate-limiting step at the extension from mismatched primer termini. Electron microscopic observation showed the accumulation of a single-stranded region at the DNA replication fork in yeast cells. For pol alpha errors, pol zeta participated in a generation of +1 frameshifts. Furthermore, in the pol1L868F strain, UV-induced mutations were lower than in the wild-type and a pol delta mutant strain (pol3-5DV), and deletion of the RAD30 gene (pol eta) suppressed this defect. These data suggest that nucleotide misincorporation by pol alpha induces exposure of single-stranded DNA, PCNA mono-ubiquitination and activates TLS pols.
authors.affiliation: Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Japan. msuzuki@med.nagoya-u.ac.jp
authors.forename: Motoshi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Niimi
authors.forename: Siripan
authors.initials: S
authors.lastname: Limsirichaikul
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomida
authors.forename: Qin
authors.initials: Q
authors.lastname: Miao Huang
authors.forename: Shunji
authors.initials: S
authors.lastname: Izuta
authors.forename: Jiro
authors.initials: J
authors.lastname: Usukura
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Itoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Hishida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Akashi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Youri
authors.initials: Y
authors.lastname: Pavlov
authors.forename: Takashi
authors.initials: T
authors.lastname: Murate
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D020137:Base Pair Mismatch; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D053843:DNA Mismatch Repair; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000648:ultrastructure; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004789:Enzyme Activation; D016368:Frameshift Mutation; D016296:Mutagenesis; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: D004277:DNA, Single-Stranded; D018809:Proliferating Cell Nuclear Antigen; D029701:Saccharomyces cerevisiae Proteins; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase