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DNA polymerase IV mediates efficient and quick recovery of replication forks stalled at N2-dG adducts.

Nucleic Acids Res.2014 Jul;42(13):8461-72. Epub 2014 Jun 23
Mio Ikeda 1 , Asako Furukohri 2 , Gaelle Philippin 3 , Edward Loechler 4 , Masahiro Tatsumi Akiyama 1 , Tsutomu Katayama 5 , Robert P Fuchs 6 , Hisaji Maki 2
Mio Ikeda 1 , Asako Furukohri 2 , Gaelle Philippin 3 , Edward Loechler 4 , Masahiro Tatsumi Akiyama 1 , Tsutomu Katayama 5 , Robert P Fuchs 6 , Hisaji Maki 2
+ et al

[No authors listed]

Author information
  • 1 Division of Integrated Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
  • 2 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.
  • 3 CRCM, CNRS, UMR7258; Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Universite, UM105, F13009 Marseille, France.
  • 4 Biology Department, Boston University, Boston, MA 02215, USA.
  • 5 Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
  • 6 CRCM, CNRS, UMR7258; Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Universite, UM105, F13009 Marseille, France furukori@bs.naist.jp.

摘要


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.

基因