DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells

• Published in: DNA repair Vol. 4; no. 1; pp. 71 - 79
• Main Authors: Zhang, Qiu-Mei, Yonekura, Shin-Ichiro, Takao, Masashi, Yasui, Akira, Sugiyama, Hiroshi, Yonei, Shuji
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 02.01.2005; Elsevier
• Subjects: 5-Formyluracil; 5-Hydroxymethyluracil; Bacteriology; Biological and medical sciences; Cloning, Molecular; Deoxyribonuclease (Pyrimidine Dimer) - genetics; Deoxyribonuclease (Pyrimidine Dimer) - metabolism; DNA glycosylase; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA Repair - genetics; DNA, Complementary - genetics; Escherichia coli; Fundamental and applied biological sciences. Psychology; Growth, nutrition, cell differenciation; hNEIL1; hNTH1; Humans; Hydrogen Peroxide - toxicity; Microbiology; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Mutation - genetics; Oligonucleotides - genetics; Oligonucleotides - metabolism; Oxidative DNA damage; Pentoxyl - analogs & derivatives; Pentoxyl - metabolism; Thymine - analogs & derivatives; Thymine - metabolism; Uracil - analogs & derivatives; Uracil - metabolism; 5-Formyluracil; hNTH1; 5-Hydroxymethyluracil; DNA glycosylase; hNEIL1; Oxidative DNA damage; Human; Oxidative stress; Enzyme; Thymine; hNTHI; Residue; DNA; Lesion; Repair
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2004.08.002

Bacteria and eukaryotes possess redundant activities that recognize and remove oxidatively damaged bases from DNA through base excision repair. DNA glycosylases excise damaged bases to initiate the base excision repair pathway. hOgg1 and hNTH1, homologues of E. coli MutM and Nth, respectively, had been identified and characterized in human cells. Recent works revealed that human cells have three orthologues of E. coli Nei, hNEIL1, hNEIL2 and hNEIL3. In the present experiments, hNEIL1 protected the E. coli nth nei mutant from lethal effect of hydrogen peroxide and high frequency of spontaneous mutations under aerobic conditions. Furthermore, hNEIL1 efficiently cleaved double stranded oligonucleotides containing 5-formyluracil (5-foU) and 5-hydroxymethyluracil (5-hmU) in vitro via β- and δ-elimination reactions. Similar activities were detected with hNTH1. These results indicate that hNEIL1 and hNTH1 are DNA glycosylases that excise 5-foU and 5-hmU as efficiently as Tg in human cells.