RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators.
APOBEC1 is the catalytic component of an RNA editing complex but shows homology to activation-induced cytidine deaminase (AID), a protein whose function is to potentiate diversification of immunoglobulin gene DNA. Here, we show that APOBEC1 and its homologs APOBEC3C and APOBEC3G exhibit potent DNA mutator activity in an E. coli assay. Indeed, like AID, these proteins appear to trigger DNA mutation through dC deamination. However, each protein exhibits a distinct local target sequence specificity. The results reveal the existence of a family of potential active dC/dG mutators, with possible implications for cancer.
Harris
Reuben S
RS
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. rsharris@mrc-lmb.cam.ac.uk
Petersen-Mahrt
Svend K
SK
Neuberger
Michael S
MS
D000071479:APOBEC-1 Deaminase; D001483:Base Sequence; D003062:Codon; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004247:DNA; D004926:Escherichia coli / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D003062:Codon; D007136:Immunoglobulins; D012313:RNA; D004247:DNA; D000071479:APOBEC-1 Deaminase; D003564:Cytidine Deaminase