Relative Binding Free Energies of Adenine and Guanine to Damaged and Undamaged DNA in Human DNA Polymerase η: Clues for Fidelity and Overall Efficiency.

ABSTRACT: Human DNA polymerase η (Pol η) plays an essential protective role against skin cancer caused by cyclobutane thymine-thymine dimers (TTDs), a frequent form of DNA damage arising from exposure to the sun. This enzyme rescues stalled replication forks at the TTDs by inserting bases opposite these DNA defects. Herein we calculate binding free energies for a free deoxyribose nucleotide triphosphate, dATP or dGTP, to Pol η complexed with undamaged or damaged DNA. The calculations indicate that the binding of dATP to the enzyme-DNA complex is thermodynamically favored for TTD-containing DNA over undamaged DNA, most likely because of more extensive hydrogen-bonding interactions between the TTD and the enzyme that hold the TTD more rigidly in place. The calculations also illustrate that dATP bindin

SUBMITTER: Ucisik MN 

PROVIDER: S-EPMC4617179 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature