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Journal of Biochemistry Advance Access published online on March 11, 2009
Journal of Biochemistry, doi:10.1093/jb/mvp043
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© The authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

PCNA Mono-ubiquitination and Activation of Translesion DNA Polymerases by DNA Polymerase {alpha}

Motoshi Suzuki1,*, Atsuko Niimi1, Siripan Limsirichaikul1, Shuta Tomida1, Qin Miao Huang1, Shunji Izuta2, Jiro Usukura3, Yasutomo Itoh4, Takashi Hishida5, Tomohiro Akashi6, Yoshiyuki Nakagawa6, Akihiko Kikuchi6, Youri Pavlov7, Takashi Murate8 and Takashi Takahashi1

1Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan;2Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan;3 EcoTopia Science Institute, Nagoya University, Nagoya, Japan;4 Division of Medical Research Engineering, Nagoya University Graduate School of Medicine, Nagoya, Japan;5Genome Dynamics Group, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;6 Division of Molecular Mycology and Medicine, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine;7 Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska, USA;8 Nagoya University School of Health Sciences, Nagoya, Japan

*To whom correspondence should be addressed. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan. Tel: +81-52-744-2455. Fax: +81-52-744-2457. E-mail: msuzuki{at}med.nagoya-u.ac.jp.

Received January 26, 2009; Accepted February 20, 2009


  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.

Key Words: DNA polymerase, translesion DNA synthesis, mutagensis, PCNA, ubiquitination


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