Structures of end products resulting from lesion processing by a DNA glycosylase/lyase.
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.
Chung
Sang J
SJ
Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, USA.
Verdine
Gregory L
GL
D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D045647:DNA Glycosylases / Q000737:chemistry* / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000737:chemistry* / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation
D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase