Orthologous mammalian APOBEC3A cytidine deaminases hypermutate nuclear DNA.

Mol Biol Evol

Molecular Retrovirology Unit, Institut Pasteur, Paris, France.

Published: February 2014

AI Article Synopsis

  • - The APOBEC3 gene cluster in humans produces enzymes that can mutate viral DNA, but recent studies show that APOBEC3A can also significantly alter nuclear DNA and cause breaks in the genome.
  • - APOBEC3A has a unique ability to deaminate a specific form of DNA called 5-methylcytidine in single-stranded DNA, making it distinct among these enzymes.
  • - Analysis of similar enzymes in various animal species (like monkeys, horses, and dogs) showed strong evolutionary conservation, indicating that their role in DNA modification is crucial and may have more benefits than risks, despite potential issues like cancer.

Article 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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http://dx.doi.org/10.1093/molbev/mst195DOI Listing

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