DNA repair function and structural modeling of a putative DNA glycosylase NEIL3

Abstract

Mammalian genes, NEIL1, NEIL2, and NEIL3, have been discovered as E.coli Nei/Fpg glycosylase family. Although repair activities of NEIL1 and NEIL2 for oxidative damage have been characterized, enzymatic activity of NEIL3 remains unclear. Here, we present a structural model for NEIL3 and examine the recombinant protein on its possible DNA repair activity. We find no clear glycosylase activity of NEIL3 as well as its DNA glycosylase domain to several types of DNA substrate containing a modified base. Nevertheless, NEIL3 retains DNA binding activity and AP-lyase activity. Moreover, NEIL3 can partially rescue E.coli nth nei mutant from hydrogen peroxide sensitivity. These results suggest that NEIL3 can work as a DNA glycosylase to repair detrimental base lesions generated by oxidative stress in vivo. [J Radiat Res 44:438 (2003)]