The Fpg/Nei Family of DNA Glycosylases: Substrates, Structures, and Search for Damage - Progress in Molecular Biology - page 71

The Fpg/Nei Family of DNA
Glycosylases: Substrates,
Structures, and Search for
Damage

Aishwarya Prakash, Sylvie
Doubli ´ , and
Susan S. Wallace
Department of Microbiology and Molecular
Genetics, The Markey Center for Molecular
Genetics, University of Vermont,
Burlington, Vermont, USA

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

II. Fpg/Nei Phylogeny . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

III. Fpg/Nei Structures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

A. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

B. Substrate Preference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

C. Comparison of Structures of the Fpg/Nei Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

IV. Glycosylases Search for Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

V. Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

During the initial stages of the base excision DNA repair pathway, DNA
glycosylases are responsible for locating and removing the majority of endoge-
nous oxidative base lesions. The bifunctional formamidopyrimidine DNA glyco-
sylase (Fpg) and endonuclease VIII (Nei) are members of the Fpg/Nei family,
one of the two families of glycosylases that recognize oxidized DNA bases, the
other being the HhH/GPD (or Nth) superfamily. Structural and biochemical
developments over the past decades have led to novel insights into the mech-
anism of damage recognition by the Fpg/Nei family of enzymes. Despite the
overall structural similarity among members of this family, these enzymes
exhibit distinct features that make them unique. This review summarizes the
current structural knowledge of the Fpg/Nei family members, emphasizes their
substrate specificities, and describes how these enzymes search for lesions.

I. Introduction

Escherichia coli formamidopyrimidine (Fapy) DNA glycosylase (Fpg) was
originally discovered in Tomas Lindahl's laboratory as a DNA glycosylase that
removes methylFapyG from alkylated DNA. 1 The E. coli gene for Fpg was