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.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

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

doi

10.1093/jb/mvp043

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

13-21

issue

1

eissn

0021-924X

issn

1756-2651

pii

mvp043

journal_volume

146

pub_type

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