Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase

被引:95
作者
Nowarski, Roni
Britan-Rosich, Elena
Shiloach, Tamar
Kotler, Moshe [1 ]
机构
[1] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Sch Med, Dept Pathol, IL-91120 Jerusalem, Israel
关键词
D O I
10.1038/nsmb.1495
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Deamination of cytidine residues in single-stranded DNA (ssDNA) is an important mechanism by which apolipoprotein B mRNA-editing, catalytic polypeptide-like (APOBEC) enzymes restrict endogenous and exogenous viruses. The dynamic process underlying APOBEC-induced hypermutation is not fully understood. Here we show that enzymatically active APOBEC3G can be detected in wild-type Vif(+) HIV-1 virions, albeit at low levels. In vitro studies showed that single enzyme-DNA encounters result in distributive deamination of adjacent cytidines. Nonlinear translocation of APOBEC3G, however, directed scattered deamination of numerous targets along the DNA. Increased ssDNA concentrations abolished enzyme processivity in the case of short, but not long, DNA substrates, emphasizing the key role of rapid intersegmental transfer in targeting the deaminase. Our data support a model by which APOBEC3G intersegmental transfer via monomeric binding to two ssDNA segments results in dispersed hypermutation of viral genomes.
引用
收藏
页码:1059 / 1066
页数:8
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