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Chem Rev. 2016 Oct 26;116(20):12688-12710. doi: 10.1021/acs.chemrev.6b00296. Epub 2016 Sep 1.

Functions and Malfunctions of Mammalian DNA-Cytosine Deaminases.

Author information

1
Department of Chemistry, Wayne State University , Detroit, Michigan 48202, United States.
2
Department of Obstetrics and Gynecology, Wayne State University , Detroit, Michigan 48201, United States.
3
Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland 20892, United States.
4
Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, Michigan 48201, United States.

Abstract

The AID/APOBEC family enzymes convert cytosines in single-stranded DNA to uracils, causing base substitutions and strand breaks. They are induced by cytokines produced during the body's inflammatory response to infections, and they help combat infections through diverse mechanisms. AID is essential for the maturation of antibodies and causes mutations and deletions in antibody genes through somatic hypermutation (SHM) and class-switch recombination (CSR) processes. One member of the APOBEC family, APOBEC1, edits mRNA for a protein involved in lipid transport. Members of the APOBEC3 subfamily in humans (APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H) inhibit infections of viruses such as HIV-1, HBV, and HCV, and retrotransposition of endogenous retroelements through mutagenic and nonmutagenic mechanisms. There is emerging consensus that these enzymes can cause mutations in the cellular genome at replication forks or within transcription bubbles depending on the physiological state of the cell and the phase of the cell cycle during which they are expressed. We describe here the state of knowledge about the structures of these enzymes, regulation of their expression, and both the advantageous and deleterious consequences of their expression, including carcinogenesis. We highlight similarities among them and present a holistic view of their regulation and function.

PMID:
27585283
PMCID:
PMC5528147
DOI:
10.1021/acs.chemrev.6b00296
[Indexed for MEDLINE]
Free PMC Article

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