Removal of oxidatively generated DNA damage by overlapping repair pathways

Vladimir Shafirovich, Nicholas E. Geacintov

Research output: Contribution to journalReview article

Abstract

It is generally believed that the mammalian nucleotide excision repair pathway removes DNA helix-distorting bulky DNA lesions, while small non-bulky lesions are repaired by base excision repair (BER). However, recent work demonstrates that the oxidativly generated guanine oxidation products, spiroimininodihydantoin (Sp), 5-guanidinohydantoin (Gh), and certain intrastrand cross-linked lesions, are good substrates of NER and BER pathways that compete with one another in human cell extracts. The oxidation of guanine by peroxynitrite is known to generate 5-guanidino-4-nitroimidazole (NIm) which is structurally similar to Gh, except that the 4-nitro group in NIm is replaced by a keto group in Gh. However, unlike Gh, NIm is an excellent substrate of BER, but not of NER. These and other related results are reviewed and discussed in this article.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalFree Radical Biology and Medicine
Volume107
DOIs
StatePublished - Jun 2017

Keywords

  • Base excision repair
  • DNA damage
  • Nucleotide excision repair
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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