Nucleic Acids Research, Vol 25, Issue 22 4557-4561, Copyright © 1997 by Oxford University Press
M Sandigursky, A Yacoub, MR Kelley, Y Xu, WA Franklin and WA Deutsch
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 beta-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 beta-elimination catalyst.
ARTICLES
The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity
Department of Radiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
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