Futile short-patch DNA base excision repair of adenine: 8-oxoguanine mispair

Keiji Hashimoto, Yohei Tominaga, Yusaku Nakabeppu, Masaaki Moriya

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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-oxo-guanine 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 3AC 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.

Original languageEnglish
Pages (from-to)5928-5934
Number of pages7
JournalNucleic acids research
Volume32
Issue number19
DOIs
Publication statusPublished - Dec 22 2004

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Adenine
DNA Repair
DNA
DNA Glycosylases
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA Ligases
Exonucleases
Guanine
DNA-Directed DNA Polymerase
8-oxo-7-hydrodeoxyguanosine
8-hydroxyguanine
DNA Replication
Ligation
Nucleotides

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Futile short-patch DNA base excision repair of adenine : 8-oxoguanine mispair. / Hashimoto, Keiji; Tominaga, Yohei; Nakabeppu, Yusaku; Moriya, Masaaki.

In: Nucleic acids research, Vol. 32, No. 19, 22.12.2004, p. 5928-5934.

Research output: Contribution to journalArticle

Hashimoto, Keiji ; Tominaga, Yohei ; Nakabeppu, Yusaku ; Moriya, Masaaki. / Futile short-patch DNA base excision repair of adenine : 8-oxoguanine mispair. In: Nucleic acids research. 2004 ; Vol. 32, No. 19. pp. 5928-5934.
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