Physical and functional interactions between Escherichia coli MutY and endonuclease VIII.
Both GO (7,8-dihydro-8-oxoguanine) and hoU (5-hydroxyuracil) are highly mutagenic because DNA polymerase frequently misincorporates adenine opposite these damaged bases. In Escherichia coli, MutY DNA glycosylase can remove misincorporated adenine opposite G or GO on the template strand during DNA replication. MutY remains bound to the product that contains an AP (apurinic/apyrimidinic) site. Endo VIII (endonuclease VIII) can remove oxidized pyrimidine and weakly remove GO by its DNA glycosylase and beta/delta-elimination activities. In the present paper, we demonstrate that Endo VIII can promote MutY dissociation from AP/G, but not from AP/GO, and can promote beta/delta-elimination on the products of MutY. MutY interacts physically with Endo VIII through its C-terminal domain. MutY has a moderate affinity for DNA containing a hoU/A mismatch, which is a substrate of Endo VIII. MutY competes with Endo VIII and inhibits Endo VIII activity on DNA that contains a hoU/A mismatch. Moreover, MutY has a weak adenine glycosylase activity on hoU/A mismatches. These results suggest that MutY may have some role in reducing the mutagenic effects of hoU.
Lu
A-Lien
AL
Department of Biochemistry and Molecular Biology and Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Lee
Chih-Yung
CY
Li
Lina
L
Li
Xianghong
X
D045647:DNA Glycosylases / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism
C453560:7,8-dihydro-8-oxoguanine; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C045975:5-hydroxyuracil; D014498:Uracil; D006147:Guanine; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468346:Nei protein, E coli; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase