Pathways for repairing and tolerating the spectrum of oxidative DNA lesions

Cancer Lett. 2012 Dec 31;327(1-2):61-72. doi: 10.1016/j.canlet.2012.02.001. Epub 2012 Feb 19.


Reactive oxygen species (ROS) arise from both endogenous and exogenous sources. These reactive molecules possess the ability to damage both the DNA nucleobases and the sugar phosphate backbone, leading to a wide spectrum of lesions, including non-bulky (8-oxoguanine and formamidopyrimidine) and bulky (cyclopurine and etheno adducts) base modifications, abasic sites, non-conventional single-strand breaks, protein-DNA adducts, and intra/interstrand DNA crosslinks. Unrepaired oxidative DNA damage can result in bypass mutagenesis during genome copying or gene expression, or blockage of the essential cellular processes of DNA replication or transcription. Such outcomes underlie numerous pathologies, including, but not limited to, carcinogenesis and neurodegeneration, as well as the aging process. Cells have adapted and evolved defense systems against the deleterious effects of ROS, and specifically devote a number of cellular DNA repair and tolerance pathways to combat oxidative DNA damage. Defects in these protective pathways trigger hereditary human diseases that exhibit increased cancer incidence, developmental defects, neurological abnormalities, and/or premature aging. We review herein classic and atypical oxidative DNA lesions, outcomes of encountering these damages during DNA replication and transcription, and the consequences of losing the ability to repair the different forms of oxidative DNA damage. We particularly focus on the hereditary human diseases Xeroderma Pigmentosum, Cockayne Syndrome and Fanconi Anemia, which may involve defects in the efficient repair of oxidative modifications to chromosomal DNA.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cockayne Syndrome / genetics
  • Cockayne Syndrome / metabolism
  • DNA Damage*
  • DNA Repair*
  • DNA Replication
  • DNA-Directed DNA Polymerase / metabolism
  • DNA-Directed RNA Polymerases / metabolism
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Heredity
  • Humans
  • Mutagenesis
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / metabolism


  • Reactive Oxygen Species
  • DNA-Directed RNA Polymerases
  • DNA-Directed DNA Polymerase