Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι.

ABSTRACT: DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn²⁺ than Mg²⁺ The human germline R96G variant impairs both Mn²⁺-dependent and Mg²⁺-dependent activities of pol ι, whereas the Δ1-25 variant selectively enhances its Mg²⁺-dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1-445) proteins. The presence of Mn²⁺ (0.15 mm) instead of Mg²⁺ (2 mm) caused a 770-fold increase in efficiency (k_pol/K_d,dCTP) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in K_d,dCTP

SUBMITTER: Choi JY 

PROVIDER: S-EPMC5076516 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature