Yale University

DNA Polymerase-γ R953C Mutant is Associated with ART-Induced Mitochondrial Toxicity.

TitleDNA Polymerase-γ R953C Mutant is Associated with ART-Induced Mitochondrial Toxicity.
Publication TypeJournal Article
Year of Publication2016
AuthorsLi, Min, Andrea C. Mislak, Yram Foli, Esinam Agbosu, Vivek Bose, Shreya Bhandari, Michal R. Szymanski, Christie K. Shumate, Whitney Y. Yin, Karen S. Anderson, and Elijah Paintsil
JournalAntimicrobial agents and chemotherapy
Date Published2016 Jul 5
ISSN1098-6596
AbstractWe found a heterozygous C2857T mutation (R953C) in Polymerase-gamma (Pol-γ) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-γ mutant binding affinity for dCTP is 8-fold less compared with that of wild-type. R953C mutant has a 4-fold decrease in discrimination of analog nucleotide relative to wild-type. R953 is located on the O-helix that forms substrate dNTP binding site; the interactions between R953 with E1056 and Y986 may stabilize the O-helix and affect polymerase activity.
DOI10.1128/AAC.00976-16
Alternate JournalAntimicrob. Agents Chemother.

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