Translesion DNA Synthesis Catalyzed by Human Pol η and Pol κ across 1,N6-Ethenodeoxyadenosine

Robert L. Levine, Holly Miller, Arthur Grollman, Eiji Ohashi, Haruo Ohmori, Chikahide Masutani, Fumio Hanaoka, Masaaki Moriya

研究成果: ジャーナルへの寄稿記事

76 引用 (Scopus)

抄録

1,N6-Ethenodeoxyadenosine, a DNA adduct generated by exogenous and endogenous sources, severely blocks DNA synthesis and induces miscoding events in human cells. To probe the mechanism for in vivo translesion DNA synthesis across this adduct, in vitro primer extension studies were conducted using newly identified human DNA polymerases (pol) η and κ, which have been shown to catalyze translesion DNA synthesis past several DNA lesions. Steady-state kinetic analyses and analysis of translesion products have revealed that the synthesis is > 100-fold more efficient with pol η than with pol κ and that both error-free and error-prone syntheses are observed with these enzymes. The miscoding events include both base substitution and frameshift mutations. These results suggest that both polymerases, particularly pol η, may contribute to the translesion DNA synthesis events observed for 1,N6-ethenodeoxyadenosine in human cells.

元の言語英語
ページ(範囲)18717-18721
ページ数5
ジャーナルJournal of Biological Chemistry
276
発行部数22
DOI
出版物ステータス出版済み - 6 1 2001
外部発表Yes

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DNA
Frameshift Mutation
Cells
DNA Adducts
DNA-Directed DNA Polymerase
Substitution reactions
Enzymes
Kinetics
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry

これを引用

Translesion DNA Synthesis Catalyzed by Human Pol η and Pol κ across 1,N6-Ethenodeoxyadenosine. / Levine, Robert L.; Miller, Holly; Grollman, Arthur; Ohashi, Eiji; Ohmori, Haruo; Masutani, Chikahide; Hanaoka, Fumio; Moriya, Masaaki.

:: Journal of Biological Chemistry, 巻 276, 番号 22, 01.06.2001, p. 18717-18721.

研究成果: ジャーナルへの寄稿記事

Levine, RL, Miller, H, Grollman, A, Ohashi, E, Ohmori, H, Masutani, C, Hanaoka, F & Moriya, M 2001, 'Translesion DNA Synthesis Catalyzed by Human Pol η and Pol κ across 1,N6-Ethenodeoxyadenosine', Journal of Biological Chemistry, 巻. 276, 番号 22, pp. 18717-18721. https://doi.org/10.1074/jbc.M102158200
Levine, Robert L. ; Miller, Holly ; Grollman, Arthur ; Ohashi, Eiji ; Ohmori, Haruo ; Masutani, Chikahide ; Hanaoka, Fumio ; Moriya, Masaaki. / Translesion DNA Synthesis Catalyzed by Human Pol η and Pol κ across 1,N6-Ethenodeoxyadenosine. :: Journal of Biological Chemistry. 2001 ; 巻 276, 番号 22. pp. 18717-18721.
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abstract = "1,N6-Ethenodeoxyadenosine, a DNA adduct generated by exogenous and endogenous sources, severely blocks DNA synthesis and induces miscoding events in human cells. To probe the mechanism for in vivo translesion DNA synthesis across this adduct, in vitro primer extension studies were conducted using newly identified human DNA polymerases (pol) η and κ, which have been shown to catalyze translesion DNA synthesis past several DNA lesions. Steady-state kinetic analyses and analysis of translesion products have revealed that the synthesis is > 100-fold more efficient with pol η than with pol κ and that both error-free and error-prone syntheses are observed with these enzymes. The miscoding events include both base substitution and frameshift mutations. These results suggest that both polymerases, particularly pol η, may contribute to the translesion DNA synthesis events observed for 1,N6-ethenodeoxyadenosine in human cells.",
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AU - Levine, Robert L.

AU - Miller, Holly

AU - Grollman, Arthur

AU - Ohashi, Eiji

AU - Ohmori, Haruo

AU - Masutani, Chikahide

AU - Hanaoka, Fumio

AU - Moriya, Masaaki

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