TY - JOUR
T1 - PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase α
AU - Suzuki, Motoshi
AU - Niimi, Atsuko
AU - Limsirichaikul, Siripan
AU - Tomida, Shuta
AU - Miao Huang, Qin
AU - Izuta, Shunji
AU - Usukura, Jiro
AU - Itoh, Yasutomo
AU - Hishida, Takashi
AU - Akashi, Tomohiro
AU - Nakagawa, Yoshiyuki
AU - Kikuchi, Akihiko
AU - Pavlov, Youri
AU - Murate, Takashi
AU - Takahashi, Takashi
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67651180879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651180879&partnerID=8YFLogxK
U2 - 10.1093/jb/mvp043
DO - 10.1093/jb/mvp043
M3 - Article
C2 - 19279190
AN - SCOPUS:67651180879
SN - 0021-924X
VL - 146
SP - 13
EP - 21
JO - Journal of Biochemistry
JF - Journal of Biochemistry
IS - 1
ER -