Distinct energetics and closing pathways for DNA polymerase beta with 8-oxoG template and different incoming nucleotides.

ABSTRACT:

Background

8-Oxoguanine (8-oxoG) is a common oxidative lesion frequently encountered by DNA polymerases such as the repair enzyme DNA polymerase beta (pol beta). To interpret in atomic and energetic detail how pol beta processes 8-oxoG, we apply transition path sampling to delineate closing pathways of pol beta 8-oxoG complexes with dCTP and dATP incoming nucleotides and compare the results to those of the nonlesioned G:dCTP and G:dATPanalogues.

Results

Our analyses show that the closing pathways of the 8-oxoG complexes are different from one another and from the nonlesioned analogues in terms of the individual transition states along each pathway, associated energies, and the stability of each pathway's closed state relative to the corresponding open state. In particular, t

SUBMITTER: Wang Y 

PROVIDER: S-EPMC1819382 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature