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Orthologous Mammalian APOBEC3A Cytidine Deaminases Hypermutate Nuclear DNA

Abstract : The human APOBEC3 gene cluster locus encodes polynucleotide cytidine deaminases. Although many act as viral restriction factors through mutation of single-stranded DNA, recent reports have shown that human APOBEC3A was capable of efficiently hypermutating nuclear DNA and inducing DNA breaks in genomic DNA. In addition, the enzyme was unique in efficiently deaminating 5-methylcytidine in single-stranded DNA. To appreciate the evolutionary relevance of these activities, we analyzed A3A-related enzymes from the rhesus and tamarin monkey, horse, sheep, dog, and panda. All proved to be orthologous to the human enzyme in all these activities revealing strong conservation more than 148 My. Hence, their singular role in DNA catabolism is a well-established mechanism probably outweighing any deleterious or pathological roles such as genomic instability and cancer formation.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03520074
Contributor : Jean-Pierre Vartanian Connect in order to contact the contributor
Submitted on : Monday, January 10, 2022 - 6:44:00 PM
Last modification on : Thursday, April 7, 2022 - 10:10:29 AM
Long-term archiving on: : Tuesday, April 12, 2022 - 12:49:35 AM

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Vincent Caval, Rodolphe Suspène, Jean Pierre Vartanian, Simon Wain-Hobson. Orthologous Mammalian APOBEC3A Cytidine Deaminases Hypermutate Nuclear DNA. Molecular Biology and Evolution, 2014, 31 (2), pp.330-340. ⟨10.1093/molbev/mst195⟩. ⟨pasteur-03520074⟩

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