期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 10, 页码 3617-3622出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0408719102
关键词
deamination; genotoxicity; alkylation
资金
- NCI NIH HHS [R01 CA097209, R37 CA018137, CA 71976, R01 CA018137, R01 CA071976, CA 18137, CA 97209] Funding Source: Medline
A recently discovered DNA repair protein of 303 aa from the archaeal organism Ferroplasma acidarmanus was studied. This protein (AGTendoV) consists of a fusion of the C-terminal active site domain of O-6-alkylguanine-DNA alkyltransferase (AGT) with an endonuclease V domain. The AGTendoV recombinant protein expressed in Escherichia coii and purified to homogeneity repaired O-6-methylguanine lesions in DNA via alkyl transfer action despite the complete absence of the N-terminal domain and some differences in key active site residues present in known AGTs. The AGTendoV recombinant protein also cleaved DNA substrates that contained the deaminated bases uracil, hypoxanthine, or xanthine in a similar manner to E. coli endonuclease V. Expression of AGTendoV in E. coli GWR109, a strain that lacks endogenous AGT activity, protected against both the killing and mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine and was more effective in preventing mutations than human alkyltransferase, suggesting that the endonuclease V activity may also repair a promutagenic lesion produced by this alkylating agent. Expression of AGTendoV in a DNA repair-deficient E. coli nfi(-)alkA(-) strain protected from spontaneous mutations arising in saturated cultures and restored the mutation frequency to that found in the nfi(+) alkA(+) strain. These results demonstrate the physiological occurrence of two completely different but functional DNA repair activities in a single polypeptide chain.
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