title: Repair and genetic consequences of endogenous DNA base damage in mammalian cells.
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.
authors.affiliation: Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK. deborah.barnes@cancer.org.uk
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Barnes
authors.forename: Tomas
authors.initials: T
authors.lastname: Lindahl
mesh_terms: D000478:Alkylation; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D003641:Deamination; D018390:Gene Targeting; D016678:Genome; D051379:Mice / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D016296:Mutagenesis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014498:Uracil / Q000378:metabolism
chemical_list: D014498:Uracil; D045647:DNA Glycosylases