Aid and Apobec Deaminases: Balancing Dna Damage in Epigenetics and Immunity

Abstract

DNA mutations and genomic recombinations are the origin of oncogenesis, yet parts of developmental programs as well as immunity are intimately linked to, or even depend on, such DNA damages. Therefore, the balance between deleterious DNA damages and organismal survival utilizing DNA editing (modification and repair) is in continuous flux. The cytosine deaminases AID/APOBEC are a DNA editing family and actively participate in various biological processes. In conjunction with altered DNA repair, the mutagenic potential of the family allows for APOBEC3 proteins to restrict viral infection and transposons propagation, while AID can induce somatic hypermutation and class switch recombination in antibody genes. On the other hand, the synergy between effective DNA repair and the nonmutagenic potential of the DNA deaminases can induce local DNA demethylation to support epigenetic cellular identity. Here, we review the current state of knowledge on the mechanisms of action of the AID/APOBEC family in immunity and epigenetics.

Keywords: :

• AID
• APOBEC
• deaminase
• DNA demethylation
• DNA repair
• epigenetics
• immunity

Acknowledgements

We are grateful for all the discussions we could have with colleagues (too numerous to mention here) in the field of AID and epigenetics regarding the various aspects of this work. We also like to thank the Petersen-Mahrt Laboratory at IFOM and in particular K-M Schmitz for valuable help and insights.

Financial disclosure & conflict of interest

The authors certify there is no affiliation with or financial involvement with any organization that could affect the objectivity of the review. D-M Franchini was supported by IFOM – Fondazione Istituto FIRC di Oncologia Molecolare fellowships, Italy. SK Petersen-Mahrt was supported by IFOM – Fondazione Istituto FIRC di Oncologia Molecolare core funding, Italy, DIVA - Discover Validation of Anticancer drugs, Lombardi, Italy, Epigenomics Flagship Project – Progetto Bandiera Epigenomica (EPIGEN), Italy, and AIRC – Italian Association for Cancer research - 13149. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.