Eukaryotic endonuclease VIII-Like proteins: New components of the base excision DNA repair system

Base excision DNA repair is necessary for removal of damaged nucleobases from the genome and their replacement with normal nucleobases. Base excision repair is initiated by DNA glycosylases, the enzymes that cleave the N-glycosidic bonds of damaged deoxynucleotides. Until recently, only eight DNA glycosylases with different substrate specificity were known in human cells. In 2002, three new human DNA glycosylases (NEIL1, NEIL2, and NEIL3) were discovered, all homologous to endonuclease VIII, a bacterial protein, which also participates in DNA repair. The role of these enzymes remains mostly unknown. In this review we discuss recent data on the substrate specificity of the NEIL enzymes, their catalytic mechanism, structure, interactions with other components of DNA repair system, and possible biological role in preventing diseases associated with DNA damage.