PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase α

Motoshi Suzuki, Atsuko Niimi, Siripan Limsirichaikul, Shuta Tomida, Qin Miao Huang, Shunji Izuta, Jiro Usukura, Yasutomo Itoh, Takashi Hishida, Tomohiro Akashi, Yoshiyuki Nakagawa, Akihiko Kikuchi, Youri Pavlov, Takashi Murate, Takashi Takahashi

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12 Citations (Scopus)

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 α, PCNA was spontaneously mono-ubiquitinated. Pol α 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 α errors, pol ζ 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 δ mutant strain (pol3-5DV), and deletion of the RAD30 gene (pol η) suppressed this defect. These data suggest that nucleotide misincorporation by pol α induces exposure of single-stranded DNA, PCNA mono-ubiquitination and activates TLS pols.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalJournal of Biochemistry
Volume146
Issue number1
DOIs
Publication statusPublished - 07-2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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    Suzuki, M., Niimi, A., Limsirichaikul, S., Tomida, S., Miao Huang, Q., Izuta, S., Usukura, J., Itoh, Y., Hishida, T., Akashi, T., Nakagawa, Y., Kikuchi, A., Pavlov, Y., Murate, T., & Takahashi, T. (2009). PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase α. Journal of Biochemistry, 146(1), 13-21. https://doi.org/10.1093/jb/mvp043