Relationship between conformational changes in pol lambda's active site upon binding incorrect nucleotides and mismatch incorporation rates.

ABSTRACT: The correct replication and repair of DNA is critical for a cell's survival. Here, we investigate the fidelity of mammalian DNA polymerase lambda (pol lambda) utilizing dynamics simulation of the enzyme bound to incorrect incoming nucleotides including A:C, A:G, A(syn):G, A:A, A(syn):A, and T:G, all of which exhibit differing incorporation rates for pol lambda as compared to A:T bound to pol lambda. The wide range of DNA motion and protein residue side-chain motions observed in the mismatched systems demonstrates distinct differences when compared to the reference (correct base pair) system. Notably, Arg517's interactions with the DNA template strand bases in the active site are more limited, and Arg517 displays increased interactions with the incorrect dNTPs. This effect suggests that Arg

SUBMITTER: Foley MC 

PROVIDER: S-EPMC2751813 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature