Miller, Freisinger, Wilson, and Kisker

DNA polymerase beta (pol b is the smallest of the four nuclear DNA polymerases. The basic structural organization of pol b: fingers, palm, and thumb subdomains, and catalytic residues are conserved among all DNA polymerases. As a constitutive repair enzyme in mammalian cells, pol b is involved in repair of many forms of base damage. The small size of this polymerase makes it amenable to crystallographic analysis and over 100 structures of pol b and its mutants have been solved. In collaboration with Sam Wilson (NIEHS) and Bill Beard, we have crystallized and determined the structure of gapped duplex DNA containing 8-oxodG in a ternary complex with pol b and with several active site mutants. These experiments provide insights into the structure of damaged DNA at the replication fork; we propose to extend this approach to DNA containing other lesions for which we have already performed a detailed kinetic analysis.

• Krahn JM, Beard WA, Miller H, Grollman AP, Wilson SH. Structure of DNA polymerase Beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential. Structure (Camb). 2003 Jan;11(1):121-7.
• Miller H, Prasad R, Wilson SH, Johnson F, Grollman AP. 8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279.Biochemistry. 2000 Feb 8;39(5):1029-33.

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