Nucleic acids research, 2003-07, Vol.31 (14), p.3893-3900
2003
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Details
- Autor(en) / Beteiligte
- Titel
- Incision at hypoxanthine residues in DNA by a mammalian homologue of the Escherichia coli antimutator enzyme endonuclease V
- Ist Teil von
- Nucleic acids research, 2003-07, Vol.31 (14), p.3893-3900
- Ort / Verlag
- England
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Deamination of DNA bases can occur spontaneously, generating highly mutagenic lesions such as uracil and hypoxanthine. In Escherichia coli two enzymes initiate repair at hypoxanthine residues in DNA. The alkylbase DNA glycosylase, AlkA, initiates repair by removal of the damaged base, whereas endonuclease V, Endo V, hydrolyses the second phosphodiester bond 3' to the lesion. We have identified and characterised a mouse cDNA with striking homology to the E.coli nfi gene, which also has significant similarities to motifs required for catalytic activity of the UvrC endonuclease. The 37-kDa mouse enzyme (mEndo V) incises the DNA strand at the second phosphodiester bond 3' to hypoxanthine- and uracil-containing nucleotides. The activity of mEndo V is elevated on single-stranded DNA substrate in vitro. Expression of the mouse protein in a DNA repair-deficient E.coli alkA nfi strain suppresses its spontaneous mutator phenotype. We suggest that mEndo V initiates an alternative excision repair pathway for hypoxanthine removal. It thus appears that mEndo V has properties overlapping the function of alkylbase DNA glycosylase (Aag) in repair of deaminated adenine, which to some extent could explain the absence of phenotypic abnormalities associated with Aag knockout in mice.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1362-4962eISSN: 1362-4962DOI: 10.1093/nar/gkg472Titel-ID: cdi_crossref_primary_10_1093_nar_gkg472
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Blotting, Northern, Conserved Sequence - genetics, Deoxyribonuclease (Pyrimidine Dimer), DNA - genetics, DNA - metabolism, DNA Repair, Endodeoxyribonucleases - genetics, Endodeoxyribonucleases - isolation & purification, Endodeoxyribonucleases - metabolism, Escherichia coli - enzymology, Escherichia coli - genetics, Female, Gene Expression Regulation, Enzymologic, Genetic Complementation Test, Humans, Hypoxanthine - metabolism, Male, Mice, Molecular Sequence Data, Mutation, Oligonucleotides - genetics, Oligonucleotides - metabolism, RNA, Messenger - genetics, RNA, Messenger - metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Suppression, Genetic, Thymine - metabolism, Uracil - metabolism