title: DNA polymerase IV mediates efficient and quick recovery of replication forks stalled at N2-dG adducts.
abstract: Escherichia coli DNA polymerase IV (Pol IV, also known as DinB) is a Y-family DNA polymerase capable of catalyzing translesion DNA synthesis (TLS) on certain DNA lesions, and accumulating data suggest that Pol IV may play an important role in copying various kinds of spontaneous DNA damage including N(2)-dG adducts and alkylated bases. Pol IV has a unique ability to coexist with Pol III on the same β clamp and to positively dissociate Pol III from β clamp in a concentration-dependent manner. Reconstituting the entire process of TLS in vitro using E. coli replication machinery and Pol IV, we observed that a replication fork stalled at (-)-trans-anti-benzo[a]pyrene-N(2)-dG lesion on the leading strand was efficiently and quickly recovered via two sequential switches from Pol III to Pol IV and back to Pol III. Our results suggest that TLS by Pol IV smoothes the way for the replication fork with minimal interruption.
authors: Division of Integrated Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
authors: Mio
authors: M
authors: Ikeda
authors: Division of Integrated Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan furukori@bs.naist.jp.
authors: Asako
authors: A
authors: Furukohri
authors: CRCM, CNRS, UMR7258; Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Universite, UM105, F13009 Marseille, France.
authors: Gaelle
authors: G
authors: Philippin
authors: Biology Department, Boston University, Boston, MA 02215, USA.
authors: Edward
authors: E
authors: Loechler
authors: Division of Integrated Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
authors: Masahiro Tatsumi
authors: MT
authors: Akiyama
authors: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Tsutomu
authors: T
authors: Katayama
authors: CRCM, CNRS, UMR7258; Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Universite, UM105, F13009 Marseille, France furukori@bs.naist.jp.
authors: Robert P
authors: RP
authors: Fuchs
authors: Division of Integrated Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan furukori@bs.naist.jp.
authors: Hisaji
authors: H
authors: Maki
mesh_terms: D001580:Benzopyrenes; D004247:DNA / Q000096:biosynthesis; D018736:DNA Adducts; D004258:DNA Polymerase III / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism*; D004261:DNA Replication; D003849:Deoxyguanosine / Q000031:analogs & derivatives*; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000378:metabolism*
chemical_list: D001580:Benzopyrenes; D018736:DNA Adducts; C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; C478198:benzo(a)pyrene N2-dG adduct; D004247:DNA; D004258:DNA Polymerase III; D019951:DNA Polymerase beta; D003849:Deoxyguanosine