The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity.

ABSTRACT: We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-?) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-? mutant binding affinity for dCTP is 8-fold less than that of the wild type. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleotides relative to the wild type. R953 is located on the "O-helix" that forms the substrate deoxynucleoside triphosphate (dNTP) binding site; the interactions of R953 with E1056 and Y986 may stabilize the O-helix and affect polymerase activity.

SUBMITTER: Li M 

PROVIDER: S-EPMC4997837 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other