Abstract
Deamination of 5-methylcytidine (5MeC) in DNA results in a G:T mismatch unlike cytidine (C) deamination which gives rise to a G:U pair. Deamination of C was generally considered to arise spontaneously. It is now clear that human APOBEC3A (A3A), a polynucleotide cytidine deaminase (PCD) with specificity for single stranded DNA, can extensively deaminate human nuclear DNA. It is shown here that A3A among all human PCDs can deaminate 5-methylcytidine in a variety of single stranded DNA substrates both in vitro and in transfected cells almost as efficiently as cytidine itself. This ability of A3A to accommodate 5-methyl moiety extends to other small and physiologically relevant substituted cytidine bases such as 5-hydroxy and 5-bromocytidine. As 5MeCpG deamination hotspots characterize many genes associated with cancer it is plausible that A3A is a major player in the onset of cancer.
Highlights
The human APOBEC3 (A3) locus encodes a seven gene cluster of polynucleotide cytidine deaminase (PCD) [1]
Human mitochondrial DNA in the cytoplasm is susceptible to cytidine deamination, probably by one or more A3 PCDs [19]
Of the eight functional human PCDs only for A3A were 3DPCR products recovered at lower temperatures, down to 77.6uC
Summary
The human APOBEC3 (A3) locus encodes a seven gene cluster of PCDs [1]. While several clearly function as restriction factors for retroviruses and DNA viruses, their roles in the absence of infection are largely undefined [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]. Human mitochondrial DNA (mtDNA) in the cytoplasm is susceptible to cytidine deamination, probably by one or more A3 PCDs [19]. As we have argued that A3A plays a physiological role in the catabolism of nuDNA [19], the question arose as to whether A3A could oxidize 5-substituted cytidine bases in DNA.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
