Repair and genetic consequences of endogenous DNA base damage in mammalian cells

Annu Rev Genet. 2004;38:445-76. doi: 10.1146/annurev.genet.38.072902.092448.

Abstract

Living organisms dependent on water and oxygen for their existence face the major challenge of faithfully maintaining their genetic material under a constant attack from spontaneous hydrolysis and active oxygen species and from other intracellular metabolites that can modify DNA bases. Repair of endogenous DNA base damage by the ubiquitous base-excision repair pathway largely accounts for the significant turnover of DNA even in nonreplicating cells, and must be sufficiently accurate and efficient to preserve genome stability compatible with long-term cellular viability. The size of the mammalian genome has necessitated an increased complexity of repair and diversification of key enzymes, as revealed by gene knock-out mouse models. The genetic instability characteristic of cancer cells may be due, in part, to mutations in genes whose products normally function to ensure DNA integrity.

Publication types

  • Review

MeSH terms

  • Alkylation
  • Animals
  • Base Composition
  • Base Sequence
  • DNA Damage*
  • DNA Glycosylases / genetics*
  • DNA Glycosylases / metabolism
  • DNA Repair*
  • Deamination
  • Gene Targeting
  • Genome*
  • Mice / genetics*
  • Mice / metabolism
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Genetic
  • Mutagenesis
  • Oxidation-Reduction
  • Oxidative Stress
  • Uracil / metabolism

Substances

  • Uracil
  • DNA Glycosylases