@article{fe2eeab8f86a4c5682894b27df6d4bb6,
title = "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-γ) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-γ 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.",
author = "Min Li and Mislak, {Andrea C.} and Yram Foli and Esinam Agbosu and Vivek Bose and Shreya Bhandari and Szymanski, {Michal R.} and Shumate, {Christie K.} and Yin, {Y. Whitney} and Anderson, {Karen S.} and Elijah Paintsil",
note = "Funding Information: We do not have a commercial or other association that might pose a conflict of interest. We are grateful to the patients at Nathan Smith Clinic, Yale-New Haven Hospital, for their cooperation. We thank all the providers and nursing staff at Nathan Smith Clinic for making the study possible. This study was supported by grants from the National Institutes of Health (KO8AI074404 and R01 HD074252 to E.P.; R01 GM49551 to K.S.A.; R01 GM083703 and R01 GM110591 to Y.W.Y.; F31 AI116322 to A.C.M.). This work, including the efforts of Elijah Paintsil, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI074404 and HD074252). This work, including the efforts of Karen S. Anderson, was funded by HHS | NIH | National Institute of General Medical Sciences (NIGMS) (GM49551). This work, including the efforts of Y. Whitney Yin, was funded by HHS | NIH | National Institute of General Medical Sciences (NIGMS) (GM083703 and GM110591). This work, including the efforts of Andrea C. Mislak, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (F31 AI116322). Publisher Copyright: Copyright {\textcopyright} 2016, American Society for Microbiology. All Rights Reserved.",
year = "2016",
month = sep,
day = "1",
doi = "10.1128/AAC.00976-16",
language = "English (US)",
volume = "60",
pages = "5608--5611",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "9",
}