8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by post-replicative base excision repair (BER) initiated by adenine DNA glycosylase, MYH, creating an apurinic (AP) site. The subsequent mechanism ensuring a dC:8-oxo-dG pair, a substrate for 8-oxoguanine DNA glycosylase (OGG1), remains to be elucidated. At the nucleotide insertion step, none of the mammalian DNA polymerases examined exclusively inserted dC opposite 8-oxo-dG that was located in a gap. AP endonuclease 1, which possesses 3'-->5' exonuclease activity and potentially serves as a proofreader, did not discriminate dA from dC that was located opposite 8-oxo-dG. However, human DNA ligases I and III joined 3'-dA terminus much more efficiently than 3'-dC terminus when paired to 8-oxo-dG. In reconstituted short-patch BER, repair products contained only dA opposite 8-oxo-dG. These results indicate that human DNA ligases discriminate dC from dA and that MYH-initiated short-patch BER is futile and hence this BER must proceed to long-patch repair, even if it is initiated as short-patch repair, through strand displacement synthesis from the ligation-resistant dC terminus to generate the OGG1 substrate, dC:8-oxo-dG pair.
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Tian, Gaochao
Katchur, Steven
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Katchur, Steven
Jiang, Yong
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Jiang, Yong
Briand, Jacques
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Briand, Jacques
Schaber, Michael
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Schaber, Michael
Kreatsoulas, Constantine
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Kreatsoulas, Constantine
Schwartz, Benjamin
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Schwartz, Benjamin
Thrall, Sara
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Thrall, Sara
Davis, Alicia
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
Davis, Alicia
Duvall, Sam
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Univ Pittsburgh, Ctr Metab & Mitochondrial Med, Dept Med, Div Cardiol, Pittsburgh, PA 15261 USA
Univ Pittsburgh, Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA 15261 USAGSK, Collegeville, PA 19426 USA
Duvall, Sam
Kaufman, Brett
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Univ Pittsburgh, Ctr Metab & Mitochondrial Med, Dept Med, Div Cardiol, Pittsburgh, PA 15261 USA
Univ Pittsburgh, Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA 15261 USAGSK, Collegeville, PA 19426 USA
Kaufman, Brett
Rumsey, William
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GSK, Collegeville, PA 19426 USAGSK, Collegeville, PA 19426 USA
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Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Nencki Inst Expt Biol, Lab Cell Signaling & Metab Disorders, PL-02093 Warsaw, Poland
Wroclaw Univ Environm & Lifesci, Dept Expt Biol, PL-02093 Wroclaw, PolandRutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Komakula, Sai Santosh Babu
Blaze, Bhavya
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Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Rutgers State Univ, Dept Nutrit Sci, New Brunswick, NJ 08901 USARutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Blaze, Bhavya
Ye, Hong
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Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USARutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Ye, Hong
Dobrzyn, Agnieszka
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Nencki Inst Expt Biol, Lab Cell Signaling & Metab Disorders, PL-02093 Warsaw, PolandRutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Dobrzyn, Agnieszka
Sampath, Harini
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Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
Rutgers State Univ, Dept Nutrit Sci, New Brunswick, NJ 08901 USA
Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Ctr Microbiome Nutr & Hlth, New Brunswick, NJ 08901 USARutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA