Base excision repair capacity in mitochondria and nuclei: tissue-specific variations.
Base excision repair is the main pathway for repair of oxidative base lesions in DNA. Mammalian cells must maintain genomic stability in their nuclear and mitochondrial genomes, which have different degrees of vulnerability to DNA damage. This study quantifies DNA glycosylase activity in mitochondria and nucleus from C57/BL 6 mouse tissues including brain, liver, heart, muscle, kidney, and testis. The activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase, and endonuclease III homologue 1 (NTH1) were measured using oligonucleotide substrates with DNA lesions specific for each glycosylase. Mitochondrial content was normalized to citrate synthase activity and mitochondrial function was assessed by measuring cytochrome c oxidase (COX) activity. In nuclear and mitochondrial extracts, the highest DNA glycosylase activities were in testis. Brain and heart, tissues with the highest oxidative load, did not have higher levels of OGG1 or NTH1 activity than muscle or kidney, which are more glycolytic tissues. In general, mitochondrial extracts have lower DNA glycosylase activity than nuclear extracts. There was no correlation between glycosylase activities in the mitochondrial extracts and COX activity, suggesting that DNA repair enzymes may be regulated by a mechanism different from this mitochondrial enzyme.
Karahalil
Bensu
B
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Hogue
Barbara A
BA
de Souza-Pinto
Nadja C
NC
Bohr
Vilhelm A
VA
D000818:Animals; D002457:Cell Extracts / Q000032:analysis; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics*; D045647:DNA Glycosylases; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000378:metabolism; D029968:Escherichia coli Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D009928:Organ Specificity; D018384:Oxidative Stress; D051981:Uracil-DNA Glycosidase
D002457:Cell Extracts; D029968:Escherichia coli Proteins; D009841:Oligonucleotides; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; C470703:Nthl1 protein, mouse; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D043382:DNA-Formamidopyrimidine Glycosylase