Mechanisms of human DNA repair: an update.
The human genome, comprising three billion base pairs coding for 30000-40000 genes, is constantly attacked by endogenous reactive metabolites, therapeutic drugs and a plethora of environmental mutagens that impact its integrity. Thus it is obvious that the stability of the genome must be under continuous surveillance. This is accomplished by DNA repair mechanisms, which have evolved to remove or to tolerate pre-cytotoxic, pre-mutagenic and pre-clastogenic DNA lesions in an error-free, or in some cases, error-prone way. Defects in DNA repair give rise to hypersensitivity to DNA-damaging agents, accumulation of mutations in the genome and finally to the development of cancer and various metabolic disorders. The importance of DNA repair is illustrated by DNA repair deficiency and genomic instability syndromes, which are characterised by increased cancer incidence and multiple metabolic alterations. Up to 130 genes have been identified in humans that are associated with DNA repair. This review is aimed at updating our current knowledge of the various repair pathways by providing an overview of DNA-repair genes and the corresponding proteins, participating either directly in DNA repair, or in checkpoint control and signaling of DNA damage.
Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany.
Markus
M
Christmann
Maja T
MT
Tomicic
Wynand P
WP
Roos
Bernd
B
Kaina
D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D004247:DNA; D011065:Poly(ADP-ribose) Polymerases