Deamination hotspots among APOBEC3 family members are defined by both target site sequence context and ssDNA secondary structure
| Autor: | Madison B. Adolph, Robin P. Love, Nazanin Mohammadzadeh, Linda Chelico, Louis M. Mansky, Yumeng Z McDaniel, Dake Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Hepatitis B virus
Retroelements Deamination DNA Single-Stranded Retrotransposon Context (language use) Biology medicine.disease_cause Protein Structure Secondary Cell Line Cytosine Deaminase 03 medical and health sciences chemistry.chemical_compound Cytidine Deaminase Genetics medicine Humans APOBEC Deaminases Molecular Biology 030304 developmental biology 0303 health sciences Mutation Binding Sites Oligonucleotide 030302 biochemistry & molecular biology Mutagenesis 3. Good health DNA-Binding Proteins chemistry RNA editing HIV-1 Nucleic Acid Conformation DNA |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3, A3) family member proteins can deaminate cytosines in single-strand (ss) DNA, which restricts human immunodeficiency virus type 1 (HIV-1), retrotransposons, and other viruses such as hepatitis B virus, but can cause a mutator phenotype in many cancers. While structural information exists for several A3 proteins, the precise details regarding deamination target selection are not fully understood. Here, we report the first parallel, comparative analysis of site selection of A3 deamination using six of the seven purified A3 member enzymes, oligonucleotides having 5′TC3′ or 5′CT3′ dinucleotide target sites, and different flanking bases within diverse DNA secondary structures. A3A, A3F and A3H were observed to have strong preferences toward the TC target flanked by A or T, while all examined A3 proteins did not show a preference for a TC target flanked by a G. We observed that the TC target was strongly preferred in ssDNA regions rather than dsDNA, loop or bulge regions, with flanking bases influencing the degree of preference. CT was also shown to be a potential deamination target. Taken together, our observations provide new insights into A3 enzyme target site selection and how A3 mutagenesis impacts mutation rates. |
| Databáze: | OpenAIRE |
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