Advantages and disadvantages of cytidine deamination.
Cytidine deamination of nucleic acids underlies diversification of Ig genes and inhibition of retroviral infection, and thus, it would appear to be vital to host defense. The host defense properties of cytidine deamination require two distinct but homologous cytidine deaminases-activation-induced cytidine deaminase and apolipoprotein B-editing cytidine deaminase, subunit 3G. Although cytidine deamination has clear benefits, it might well have biological costs. Uncontrolled cytidine deamination might generate misfolded polypeptides, dominant-negative proteins, or mutations in tumor suppressor genes, and thus contribute to tumor formation. How cytidine deaminases target a given nucleic acid substrate at specific sequences is not understood, and what protects cells from uncontrolled mutagenesis is not known. In this paper, I shall review the functions and regulation of activation-induced cytidine deaminase and apolipoprotein B-editing cytidine deaminase, subunit 3G, and speculate about the basis for site specificity vis-à-vis generalized mutagenesis.
Cascalho
Marilia
M
Transplantation Biology, and Departments of Immunology, Surgery, and Pediatrics, Mayo Clinic, Rochester, MN 55905, USA. cascalho.marilia@mayo.edu
D000071479:APOBEC-1 Deaminase; D000071480:APOBEC-3G Deaminase; D000818:Animals; D001483:Base Sequence; D003562:Cytidine / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000502:physiology*; D043525:Cytosine Deaminase / Q000502:physiology*; D005803:Genes, Immunoglobulin; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000209:etiology; D009700:Nucleoside Deaminases; D021381:Protein Transport; D011506:Proteins / Q000502:physiology*; D012097:Repressor Proteins; D012192:Retroviridae Infections / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D011506:Proteins; D012097:Repressor Proteins; D003562:Cytidine; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase