Structures of end products resulting from lesion processing by a DNA glycosylase/lyase

Chem Biol. 2004 Dec;11(12):1643-9. doi: 10.1016/j.chembiol.2004.09.014.

Abstract

DNA glycosylase/lyases initiate the repair of damaged nucleobases in the genome by catalyzing excision of aberrant nucleobases and nicking of the lesion-containing DNA strand. Nearly all of these proteins have the unusual property of remaining tightly bound in vitro to the end products of the reaction cascade. We have taken advantage of this property to crystallize and structurally characterize the end product resulting from complete DNA processing by a catalytically active mutant form of human 8-oxoguanine DNA glycosylase (D268E hOgg1). The resulting structure is consistent with the currently accepted catalytic mechanism for the protein. Unexpectedly, however, soaking of a nucleobase analog into the crystals results in religation of the DNA backbone in situ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / metabolism
  • DNA Glycosylases / chemistry*
  • DNA Glycosylases / metabolism
  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / chemistry*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
  • Guanine / analogs & derivatives
  • Guanine / chemistry
  • Guanine / metabolism
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Nucleic Acid Conformation

Substances

  • Guanine
  • DNA
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase

Associated data

  • PDB/1M3H
  • PDB/1M3Q