Targeted Deletion of mNth1 Reveals a Novel DNA Repair Enzyme Activity
AUTOR(ES)
Ocampo, Maria T. A.
FONTE
American Society for Microbiology
RESUMO
DNA N-glycosylase/AP (apurinic/apyrimidinic) lyase enzymes of the endonuclease III family (nth in Escherichia coli and Nth1 in mammalian organisms) initiate DNA base excision repair of oxidized ring saturated pyrimidine residues. We generated a null mouse (mNth1−/−) by gene targeting. After almost 2 years, such mice exhibited no overt abnormalities. Tissues of mNth1−/− mice contained an enzymatic activity which cleaved DNA at sites of oxidized thymine residues (thymine glycol [Tg]). The activity was greater when Tg was paired with G than with A. This is in contrast to Nth1, which is more active against Tg:A pairs than Tg:G pairs. We suggest that there is a back-up mammalian repair activity which attacks Tg:G pairs with much greater efficiency than Tg:A pairs. The significance of this activity may relate to repair of oxidized 5-methyl cytosine residues (5meCyt). It was shown previously (S. Zuo, R. J. Boorstein, and G. W. Teebor, Nucleic Acids Res. 23:3239-3243, 1995) that both ionizing radiation and chemical oxidation yielded Tg from 5meCyt residues in DNA. Thus, this previously undescribed, and hence novel, back-up enzyme activity may function to repair oxidized 5meCyt residues in DNA while also being sufficient to compensate for the loss of Nth1 in the mutant mice, thereby explaining the noninformative phenotype.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=134015Documentos Relacionados
- Targeted disruption of NBS1 reveals its roles in mouse development and DNA repair
- Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein
- Targeted deletion of CX3CR1 reveals a role for fractalkine in cardiac allograft rejection
- Targeted Deletion Reveals an Essential Function for the Telomere Length Regulator Trf1
- Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme.