Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase γ
SE Lim, WC Copeland - Journal of Biological Chemistry, 2001 - ASBMB
Mitochondrial toxicity can result from antiviral nucleotide analog therapy used to control
human immunodeficiency virus type 1 infection. We evaluated the ability of such analogs to
inhibit DNA synthesis by the human mitochondrial DNA polymerase (pol γ) by comparing the
insertion and exonucleolytic removal of six antiviral nucleotide analogs. Apparent steady-
stateK m and k cat values for insertion of 2′, 3′-dideoxy-TTP (ddTTP), 3′-azido-TTP (AZT-
TP), 2′, 3′-dideoxy-CTP (ddCTP), 2′, 3′-didehydro-TTP (D4T-TP),(-)-2′, 3′-dideoxy …
human immunodeficiency virus type 1 infection. We evaluated the ability of such analogs to
inhibit DNA synthesis by the human mitochondrial DNA polymerase (pol γ) by comparing the
insertion and exonucleolytic removal of six antiviral nucleotide analogs. Apparent steady-
stateK m and k cat values for insertion of 2′, 3′-dideoxy-TTP (ddTTP), 3′-azido-TTP (AZT-
TP), 2′, 3′-dideoxy-CTP (ddCTP), 2′, 3′-didehydro-TTP (D4T-TP),(-)-2′, 3′-dideoxy …
