Physical and functional interactions between Escherichia coli MutY and endonuclease VIII

A. Lien Lu, Chih Yung Lee, Lina Li, Xianghong Li

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)381-387
Number of pages7
JournalBiochemical Journal
Volume393
Issue number1
DOIs
StatePublished - Jan 1 2006

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

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