Journal of the American Chemical Society, Vol.118, No.44, 10684-10692, 1996
Specific Recognition of Substrate-Analogs by the DNA Mismatch Repair Enzyme Muty
The DNA repair enzyme MutY plays an important role in the prevention of DNA mutations caused by the oxidatively damaged lesion 7,8-dihydro-8-oxo-2’-deoxyguanosine (OG) by removal of misincorporated adenine residues in OG:A mismatched base pairs using N-glycosylase activity. MutY also has glycosylase activity toward adenine in the mismatched base-pairs G:A and C:A. We have investigated the interaction of MutY with DNA duplexes containing the 2’-deoxyadenosine (A) analogs 2’-deoxytubercidin (7-deaza-2’-deoxyadenosine, Z) and 2’-deoxyformycin A (F). Both F and Z should effectively mimic the recognition properties of A but be resistant to the glycosylase activity of MutY, owing to their structural properties. Thus, these derivatives will provide a method for forming a stable MutY-substrate analog complex amenable to structural and biochemical investigation. We find that oligonucleotide duplexes containing OG/G:F and OG/G:Z base-pairs are not substrates for MutY as expected.
Keywords:ESCHERICHIA-COLI MUTY;G-A MISPAIRS;CRYSTAL-STRUCTURE;8-HYDROXYGUANINE 7;8-DIHYDRO-8-OXOGUANINE;FORMYCIN 5’-PHOSPHATE;CATALYTIC MECHANISM;ENDONUCLEASE-III;AMP NUCLEOSIDASE;MINOR-GROOVE;BASE-PAIRS