Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms

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Human cells possess a family of seven DNA-modification enzymes, termed APOBEC3, that function as part of our innate immune system. The enzymes modify cytosine in DNA which induces mutations. There are particular enzymes, APOBEC3D, APOBEC3F, APOBEC3G and APOBEC3H, that appear to be most relevant to restricting HIV-1 replication in CD4+ T cells using this mutagenic mechanism, if they can avoid degradation that is induced by the HIV-1 protein Vif. There has been little biochemical analysis of APOBEC3 enzymes other than APOBEC3G in terms of the mechanism by which these enzymes search DNA for target cytosines to deaminate. We conducted a biochemical analysis of APOBEC3F. We found that while APOBEC3G uses 1-dimensional sliding and 3-dimensional translocations, APOBEC3F is restricted to 3-dimensional translocations. This makes the searching mechanism of APOBEC3F superficial and detrimental to the induction of a large number of mutations. In addition, gene inactivation was less likely to occur upon deamination of the target motif of APOBEC3F (5′TTC), in comparison to the target motif of APOBEC3G (5′CCC). All together the data support a model in which the way these enzymes scan DNA can predict the magnitude of mutagenesis induced and the target motif can predict ability to cause gene inactivation.

Vyšlo v časopise: Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004024
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004024

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