Deamination hotspots among APOBEC3 family members are defined by both target site sequence context and ssDNA secondary structure.

McDaniel, Yumeng Z; Wang, Dake; Love, Robin P; Adolph, Madison B; Mohammadzadeh, Nazanin; Chelico, Linda; Mansky, Louis M

McDaniel, Yumeng Z; Wang, Dake; Love, Robin P; Adolph, Madison B; Mohammadzadeh, Nazanin; Chelico, Linda; Mansky, Louis M.

Afiliación

McDaniel YZ; Veterinary Medicine Graduate Program, University of Minnesota, Minneapolis, MN 55455 USA.
Wang D; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455 USA.
Love RP; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455 USA.
Adolph MB; Pharmacology Graduate Program, University of Minnesota, Minneapolis, MN 55455 USA.
Mohammadzadeh N; Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
Chelico L; Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.
Mansky LM; Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, Canada.

Nucleic Acids Res ; 48(3): 1353-1371, 2020 02 20.

Article en En | MEDLINE | ID: mdl-31943071

RESUMEN

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.

Asunto(s)

Citidina Desaminasa/genética; ADN de Cadena Simple/genética; Proteínas de Unión al ADN/genética; Desaminación/genética; Desaminasas APOBEC; Sitios de Unión/genética; Línea Celular; Citidina Desaminasa/química; Citosina Desaminasa/química; Citosina Desaminasa/genética; ADN de Cadena Simple/química; Proteínas de Unión al ADN/química; VIH-1/genética; VIH-1/patogenicidad; Virus de la Hepatitis B/genética; Humanos; Mutagénesis/genética; Conformación de Ácido Nucleico; Estructura Secundaria de Proteína; Retroelementos/genética

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN de Cadena Simple / Citidina Desaminasa / Desaminación / Proteínas de Unión al ADN Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido

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