The discovery of a new family of mammalian enzymes for repair of oxidatively damaged DNA, and its physiological implications.
Oxidatively damaged bases in the genome are likely to be responsible for mutations leading to sporadic carcinogenesis. Two structurally similar DNA glycosylases, NTH1 and OGG1, which are able to excise most of these damaged bases, were identified previously in mammalian cells. A distinct family, consisting of two human DNA glycosylases orthologous to enzymes in Escherichia coli, has recently been characterized; they have overlapping substrate ranges with NTH1 and OGG1. The presence of multiple enzymes with potential back-up functions underscores the importance of removing both endogenously and exogenously generated oxidatively damaged bases from the genome, and may explain why no cancer or other disease phenotype has so far been linked to the deficiency of a single DNA glycosylase.
Hazra
Tapas K
TK
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX 77555, USA.
Izumi
Tadahide
T
Kow
Y Wah
YW
Mitra
Sankar
S
D000818:Animals; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D018384:Oxidative Stress
D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases