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

The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity.
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Li M, Mislak AC, Foli Y, Agbosu E, Bose V, Bhandari S, Szymanski MR, Shumate CK, Yin YW, Anderson KS, Paintsil E,


Li M, Mislak AC, Foli Y, Agbosu E, Bose V, Bhandari S, Szymanski MR, Shumate CK, Yin YW, Anderson KS, Paintsil E, (click to view)

Li M, Mislak AC, Foli Y, Agbosu E, Bose V, Bhandari S, Szymanski MR, Shumate CK, Yin YW, Anderson KS, Paintsil E,

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Antimicrobial agents and chemotherapy 2016 08 2260(9) 5608-11 doi 10.1128/AAC.00976-16

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.

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