Biochemical Basis of APOBEC3 Deoxycytidine Deaminase Activity on Diverse DNA Substrates

• DOI: 10.1021/acsinfecdis.7b00221
• Publication Date: 2018-01-19T02:09:17Z
• Authors: Madison B. Adolph; Robin P. Love; Linda Chelico
• Keywords: Deamination; Processivity; APOBEC; Retrotransposon; APOBEC3G; DNA demethylation; Cytosine

The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes contains single-stranded polynucleotide cytidine deaminases. These catalyze the deamination in RNA or DNA, which forms uracil. From this 11 member enzyme humans, DNA by seven APOBEC3 members is considered here. has many roles, such as restricting endogenous and exogenous retrovirus replication retrotransposon insertion events reducing DNA-induced inflammation. Similar to other APOBEC members, are a double-edged sword that can cytosine genomic results potential instability due mutagenic fates uracil DNA. Here, we discuss how these find their substrate different biological contexts during human immunodeficiency virus (HIV) proviral synthesis, retrotransposition LINE-1 element, "off-target" substrate. must be able efficiently deaminate transiently available reverse transcription, replication, transcription. Specific biochemical characteristics promote each situation increase efficiency through processivity, rapid cycling between substrates, oligomerization state. use data clarify functions alignment with cellular discussed. Models bridge knowledge from biochemical, structural, single molecule experiments presented.