Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Base excision repair of adenine/8-oxoguanine mispairs by an aphidicolin-sensitive DNA polymerase in human cell extracts

Oncogene volume 21, pages 5204–5212 (2002)Cite this article

Abstract

Replication of DNA containing 8-oxo-7,8-dihydroguanine (8oxoG) can generate 8oxoG/A base pairs which, if uncorrected, lead to G→T transversions. It is generally accepted that the repair of these promutagenic base pairs in human cells is initiated by the MutY DNA glycosylase homolog (hMYH). Here we provide biochemical evidence that human cell extracts perform base excision repair (BER) on both DNA strands of an 8oxoG/A mismatch. At early repair times the specificity of nucleotide incorporation indicates a preferential insertion of C opposite 8oxoG leading to the formation of 8oxoG/C pairs. This is followed by repair synthesis on the opposite DNA strand that is consistent with hOGG1-mediated correction of 8oxoG/C to G/C. Repair synthesis on either strand is completely inhibited by aphidicolin suggesting that a replicative DNA polymerase is involved in the gap filling. This is the first demonstration that repair of 8oxoG/A base pairs is by two BER events likely mediated by Polδ/ε. We suggest that the Polδ/ε-mediated BER is the general mode of repair when BER lesions are formed at replication forks.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Au KG, Clark S, Miller JH, Modrich P . 1989 Proc. Natl. Acad. Sci. USA 86: 8877–8881

  • Boiteux S, Radicella JP . 1999 Biochimie 81: 59–67

  • Boiteux S, Radicella JP . 2000 Arch. Biochem. Biophys. 377: 1–8

  • Boldogh I, Milligan D, Lee MS, Bassett H, Lloyd RS, McCullough AK . 2001 Nucleic Acids Res. 29: 2802–2809

  • Caldecott KW . 2001 Bioessays 23: 447–455

  • Colussi C, Parlanti E, Degan P, Aquilina G, Barnes D, Macpherson P, Karran P, Crescenzi M, Dogliotti E, Bignami M . 2002 Curr. Biol. 12: 1–20

  • DeMott MS, Zigman S, Bambara RA . 1998 J. Biol. Chem. 273: 27492–27498

  • DeWeese TL, Shipman JM, Larrier NA, Buckley NM, Kidd LR, Groopman JD, Cutler RG, Te Riele H, Nelson WG . 1998 Proc. Natl. Acad. Sci. USA 95: 11915–11920

  • Dianov G, Bischoff C, Piotrowski J, Bohr VA . 1998 J. Biol. Chem. 278: 33511–33516

  • Dianov G, Prasad R, Wilson S, Bohr V . 1999a JBC 274: 13741–13743

  • Dianov GL, Jensen BR, Kenny MK, Bohr VA . 1999b Biochemistry 38: 11021–11025

  • Dizdaroglu M, Laval J, Boiteux S . 1993 Biochemistry 32: 12105–12111

  • Dogliotti E, Fortini P, Pascucci B, Parlanti E . 2001 Prog. Nucleic Acid Res. Mol. Biol. 68: 1–28

  • Efrati E, Tocco G, Eritja R, Wilson SH, Goodman MF . 1999 J. Biol. Chem. 274: 15920–15926

  • Einolf HJ, Guengerich FP . 2001 J. Biol. Chem. 276: 3764–3771

  • Fortini P, Parlanti E, Sidorkina OM, Laval J, Dogliotti E . 1999 J. Biol. Chem. 274: 15230–15236

  • Fortini P, Pascucci B, Parlanti E, Sobol RW, Wilson SH, Dogliotti E . 1998 Biochemistry 37: 3575–3580

  • Frosina G, Fortini P, Rossi O, Carrozzino F, Raspaglio G, Cox LS, Lane DP, Abbondandolo A, Dogliotti E . 1996 J. Biol. Chem. 271: 9573–9578

  • Gary R, Kim K, Cornelius HL, Park MS, Matsumoto Y . 1999 J. Biol. Chem. 274: 4354–4363

  • Gerlach VL, Feaver WJ, Fischhaber PL, Friedberg EC . 2001 J. Biol. Chem. 276: 92–98

  • Haracska L, Yu SL, Johnson RE, Prakash L, Prakash S . 2000 Nat. Genet. 25: 458–461

  • Laval J, Jurado J, Saparbaev M, Sidorkina O . 1998 Mutat. Res. 402: 93–102

  • Le Page F, Kwoh EE, Avrutskaya A, Gentil A, Leadon SA, Sarasin A, Cooper PK . 2000 Cell 101: 159–171

  • Leadon SA, Avrutskaya AV . 1997 Cancer Res. 57: 3784–3791

  • Li X, Wright PM, Lu AL . 2000 J. Biol. Chem. 275: 8448–8455

  • Masutani C, Araki M, Yamada A, Kusumoto R, Nogimori T, Maekawa T, Iwai S, Hanaoka F . 1999 EMBO J. 18: 3491–3501

  • McGoldrick JP, Yeh Y-C, Solomon M, Essigmann JM, Lu A-L . 1995 Mol. Cell. Biol. 15: 989–996

  • Michaels ML, Cruz C, Grollman AP, Miller JH . 1992a Proc. Natl. Acad. Sci. USA 89: 7022–7025

  • Michaels ML, Tchou J, Grollman AP, Miller JH . 1992b Biochemistry 31: 10964–10968

  • Nelson JR, Lawrence CW, Hinkle DC . 1996 Science 272: 1646–1649

  • Nghiem Y, Cabrera M, Cupples CG, Miller JH . 1988 Proc. Natl. Acad. Sci. USA 85: 2709–2713

  • Nilsen H, Rosewell I, Robins P, Skjelbred CF, Andersen S, Slupphaug G, Daly G, Krokan HE, Lindahl T, Barnes DE . 2000 Mol. Cell. Biol. 5: 1059–1065

  • Otterlei M, Warbrick E, Nagelhus TA, Haug T, Slupphaug G, Akbari M, Aas PA, Steinsbekk K, Bakke O, Krokan HE . 1999 EMBO J. 18: 3834–3844

  • Parker A, Gu Y, Mahoney W, Lee SH, Singh KK, Lu AL . 2001 J. Biol. Chem. 276: 5547–5555

  • Porello SL, Leyes AE, David SS . 1998 Biochemistry 37: 14756–14764

  • Prasad R, Dianov GL, Bohr VA, Wilson SH . 2000 J. Biol. Chem. 275: 4460–4466

  • Sakumi K, Furuichi M, Tsuzuki T, Kakuma T, Kawabata S, Maki H, Sekiguchi M . 1993 J. Biol. Chem. 268: 23524–23530

  • Shibutani S, Takeshita M, Grollman AP . 1991 Nature 349: 431–434

  • Slupska MM, Baikalov C, Luther WM, Chiang JH, Wei YF, Miller JH . 1996 J. Bacteriol. 178: 3885–3892

  • Slupska MM, Luther WM, Chiang JH, Yang H, Miller JH . 1999 J. Bacteriol. 181: 6210–6213

  • Takao M, Zhang QM, Yonei S, Yasui A . 1999 Nucleic Acids Res. 27: 3638–3644

  • Taylor RM, Moore DJ, Whitehouse J, Johnson P, Caldecott KW . 2000 Mol. Cell. Biol. 20: 735–740

  • Tchou J, Bodepudi V, Shibutani S, Antoshechkin I, Miller J, Grollman AP, Johnson F . 1994 J. Biol. Chem. 269: 15318–15324

  • Tissier A, McDonald JP, Frank EG, Woodgate R . 2000 Genes Dev. 14: 1642–1650

  • Tom S, Henricksen LA, Park MS, Bambara RA . 2001 J. Biol. Chem. 276: 24817–24825

  • Weiser T, Gassmann M, Thommes P, Ferrari E, Hafkemeyer P, Hubscher U . 1991 J. Biol. Chem. 266: 10420–10428

  • Yang H, Clendenin WM, Wong D, Demple B, Slupska MM, Chiang JH, Miller JH . 2001 Nucleic Acids Res. 29: 743–752

  • Yeh Y, Chang D, Masin J, Lu A . 1991 J. Biol. Chem. 266: 6480–6484

  • Zhang Y, Yuan F, Wu X, Taylor JS, Wang Z . 2001 Nucleic Acids Res. 29: 928–935

  • Zharkov DO, Grollman AP . 1998 Biochemistry 37: 12384–12394

Download references

Author information

Authors and Affiliations

  1. Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanita', Viale Regina Elena 299, Rome, 00161, Italy

    Eleonora Parlanti, Paola Fortini & Eugenia Dogliotti

  2. Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, UK

    Peter Macpherson

  3. UMR 1772 CNRS, Groupe Reparation de l'ADN, Institut Gustave Roussy, 39 Rue C. Desmulins, Villejuif Cedex, 94805, France

    Jacques Laval

Authors
  1. Eleonora Parlanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Fortini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Macpherson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacques Laval
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eugenia Dogliotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eugenia Dogliotti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parlanti, E., Fortini, P., Macpherson, P. et al. Base excision repair of adenine/8-oxoguanine mispairs by an aphidicolin-sensitive DNA polymerase in human cell extracts. Oncogene 21, 5204–5212 (2002). https://doi.org/10.1038/sj.onc.1205561

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205561

Keywords

This article is cited by

Search

Advanced search

Quick links

  NODES
chat 1
INTERN 1
twitter 1