Article,

APOBEC3G DNA deaminase acts processively 3' $\to$ 5' on single-stranded DNA

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Nat Struct Mol Biol, 13 (5): 392--399 (May 2006)

Abstract

Akin to a ‘Trojan horse,’ APOBEC3G DNA deaminase is encapsulated by the HIV virion. APOBEC3G facilitates restriction of HIV-1 infection in T cells by deaminating cytosines in nascent minus-strand complementary DNA. Here, we investigate the biochemical basis for C-U targeting. We observe that APOBEC3G binds randomly to single-stranded DNA, then jumps and slides processively to deaminate target motifs. When confronting partially double-stranded DNA, to which APOBEC3G cannot bind, sliding is lost but jumping is retained. APOBEC3G shows catalytic orientational specificity such that deamination occurs predominantly 3¢-5¢ without requiring hydrolysis of a nucleotide cofactor. Our data suggest that the G-A mutational gradient generated in viral genomic DNA in vivo could result from an intrinsic processive directional attack by APOBEC3G on single- stranded cDNA

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