RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators

Reuben S. Harris, Svend K. Petersen-Mahrt, Michael S. Neuberger

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1247-1253
Number of pages7
JournalMolecular Cell
Volume10
Issue number5
DOIs
StatePublished - Nov 1 2002

Bibliographical note

Funding Information:
We thank those who provided DNA clones or bacterial strains, including the E. coli Genetic Stock Center (CGSC). R.S.H. and S.K.P.M. were supported in part by the Leukaemia Research Fund and the Arthritis Research Campaign, respectively. R.S.H. also expresses gratitude to T. Pollock for expert technical assistance and to Sidney Sussex College for support. We thank R. Beale, J. Di Noia, K.J. Patel, C. Rada, J. Sale, and G.T. Williams for discussions.

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