title: Structural design of a eukaryotic DNA repair polymerase: DNA polymerase beta.
abstract: DNA polymerase beta, the smallest eukaryotic DNA polymerase, is designed to synthesize DNA in short DNA gaps during DNA repair. It is composed of two specialized domains that contribute essential enzymatic activities to base excision repair (BER). Its amino-terminal domain possesses a lyase activity necessary to remove the 5'-deoxyribose phosphate (dRP) intermediate generated during BER. Removal of the dRP moiety is often the rate-limiting step during BER. Failure to remove this group may initiate alternate BER pathways. The larger polymerase domain has nucleotidyl transferase activity. This domain has a modular organization with sub-domains that bind duplex DNA, catalytic metals, and the correct nucleoside triphosphate in a template-dependent manner. X-ray crystal structures of DNA polymerase beta, with and without bound substrates, has inferred that domain, sub-domain, and substrate conformational changes occur upon ligand binding. Many of these conformational changes are distinct from those observed in structures of other DNA polymerases. This review will examine the structural aspects of DNA polymerase beta that facilitate its role in BER.
authors.affiliation: Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Beard
authors.forename: S H
authors.initials: SH
authors.lastname: Wilson
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000502:physiology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005057:Eukaryotic Cells / Q000201:enzymology*; D006801:Humans; D008190:Lyases / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA; D019951:DNA Polymerase beta; D008190:Lyases