CRYSTAL-STRUCTURE OF RAT DNA-POLYMERASE-BETA - EVIDENCE FOR A COMMON POLYMERASE MECHANISM

Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton doma in is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Kl enow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse tran scriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-k ilodalton domain is attached to the fingers subdomain by a flexible hi nge. The two invariant aspartates found in all polymerase sequences an d implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicat ing that the polymerases have maintained, or possibly re-evolved, a co mmon nucleotidyl transfer mechanism. The location of Mn2+ and deoxyade nosine triphosphate in pot beta confirms the role of the invariant asp artates in metal ion and deoxynucleoside triphosphate binding.