The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity

Margarita Sandigursky, Adly Yacoub, Mark Kelley, Yi Xu, William A. Franklin, Walter A. Deutsch

Research output: Contribution to journalArticle

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Abstract

The yeast OGG1 gene was recently cloned and shown to encode a protein that possesses N-glycosylase/AP lyase activities for the repair of oxidatively damaged DNA at sites of 7,8-dihydro-8-oxoguanine (8-oxoguanine). Similar activities have been identified for Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) and Drosophila ribosomal protein S3. Both Fpg and S3 also contain a deoxyribophosphodiesterase (dRpase) activity that removes 2-deoxyribose-5-phosphate at an incised 5' apurinic/apyrimidinic (AP) sites via a β-elimination reaction. Drosophila S3 also has an additional activity that removes trans-4-hydroxy-2-pentenal-5-phosphate at a 3' incised AP site by a Mg2+-dependent hydrolytic mechanism. In view of the substrate similarities between Ogg1, Fpg and S3 at the level of base excision repair, we examined whether Ogg1 also contains dRpase activities. A glutathione S-transferase fusion protein of Ogg1 was purified and subsequently found to efficiently remove sugar-phosphate residues at incised 5' AP sites. Activity was also detected for the Mg2+-dependent removal of trans-4-hydroxy-2-pentenal-5-phosphate at 3' incised AP sites and from intact AP sites. Previous studies have shown that DNA repair proteins that possess AP lyase activity leave an inefficient DNA terminus for subsequent DNA synthesis steps associated with base excision repair. However, the results presented here suggest that in the presence of MgCl2, Ogg1 can efficiently process 8-oxoguanine so as to leave a one nucleotide gap that can be readily filled in by a DNA polymerase, and importantly, does not therefore require additional enzymes to process trans-4-hydroxy-2-pentenal-5-phosphate left at a 3' terminus created by a β-elimination catalyst.

Original languageEnglish
Pages (from-to)4557-4561
Number of pages5
JournalNucleic Acids Research
Volume25
Issue number22
StatePublished - 1997

Fingerprint

DNA-Formamidopyrimidine Glycosylase
DNA Glycosylases
DNA Repair
Lyases
Yeasts
Phosphates
DNA
Sugar Phosphates
Drosophila Proteins
Proteins
Magnesium Chloride
DNA-Directed DNA Polymerase
Glutathione Transferase
Drosophila
Nucleotides
Escherichia coli
Enzymes
Genes
8-hydroxyguanine
DNA deoxyribophosphodiesterase

ASJC Scopus subject areas

  • Genetics

Cite this

Sandigursky, M., Yacoub, A., Kelley, M., Xu, Y., Franklin, W. A., & Deutsch, W. A. (1997). The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity. Nucleic Acids Research, 25(22), 4557-4561.

The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity. / Sandigursky, Margarita; Yacoub, Adly; Kelley, Mark; Xu, Yi; Franklin, William A.; Deutsch, Walter A.

In: Nucleic Acids Research, Vol. 25, No. 22, 1997, p. 4557-4561.

Research output: Contribution to journalArticle

Sandigursky, M, Yacoub, A, Kelley, M, Xu, Y, Franklin, WA & Deutsch, WA 1997, 'The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity', Nucleic Acids Research, vol. 25, no. 22, pp. 4557-4561.
Sandigursky, Margarita ; Yacoub, Adly ; Kelley, Mark ; Xu, Yi ; Franklin, William A. ; Deutsch, Walter A. / The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity. In: Nucleic Acids Research. 1997 ; Vol. 25, No. 22. pp. 4557-4561.
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