Abstract
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 β/δ- 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 β/δ-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.
Original language | English (US) |
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Pages (from-to) | 381-387 |
Number of pages | 7 |
Journal | Biochemical Journal |
Volume | 393 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2006 |
Externally published | Yes |
Keywords
- 7,8-Dihydro-8-oxoguanine (GO)
- DNA glycosylase
- Endonuclease VIII
- MutY
- Oxidized pyrimidine
- Protein-protein interaction
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology