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.
Figure 1.
Figure 1. Proposed Mechanism for hOgg1-Catalyzed Excision
of 8-Oxoguanine (oxoG) and Cleavage of the DNA Strand
Figure 2.
Figure 2. Active Site Structure of the End-Product Complex
The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2004,
11,
1643-1649)
copyright 2004.
