期刊
NATURE REVIEWS GENETICS
卷 23, 期 8, 页码 505-518出版社
NATURE PORTFOLIO
DOI: 10.1038/s41576-022-00459-8
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资金
- European Research Council (ERC) [649019]
- German Research Foundation (DFG) [SPP1784, TRR319-RMaP]
- European Research Council (ERC) [649019] Funding Source: European Research Council (ERC)
The AID/APOBEC polynucleotide cytidine deaminases have diverse functions as both DNA mutators and RNA editors, and their strict functional classification needs to be reconsidered. Understanding the structural differences and similarities between these enzymes will contribute to improving the design of programmable base editors for therapeutic purposes.
The AID/APOBEC polynucleotide cytidine deaminases have historically been classified as either DNA mutators or RNA editors based on their first identified nucleic acid substrate preference. DNA mutators can generate functional diversity at antibody genes but also cause genomic instability in cancer. RNA editors can generate informational diversity in the transcriptome of innate immune cells, and of cancer cells. Members of both classes can act as antiviral restriction factors. Recent structural work has illuminated differences and similarities between AID/APOBEC enzymes that can catalyse DNA mutation, RNA editing or both, suggesting that the strict functional classification of members of this family should be reconsidered. As many of these enzymes have been employed for targeted genome (or transcriptome) editing, a more holistic understanding will help improve the design of therapeutically relevant programmable base editors. In this Perspective, Pecori et al. provide an overview of the AID/APOBEC cytidine deaminase family, discussing key structural features, how they contribute to viral and tumour evolution and how they can be harnessed for (potentially therapeutic) base-editing purposes.
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