Evidence already exists that the activation-induced deaminase (AID)/APOBEC family
constitutes a set of differentially expressed enzymes capable of deaminating cytosines
(C to U) in single-stranded DNA (ssDNA) and that they are potentially powerful mutagens.
The mutagenic processes involved are believed to be activated in many nonlymphoid
tissue types—for example, initiating some cancers and/or leading to further somatic
mutagenesis. To investigate the extent that codon context might be important in influencing
the likely location of TP53 mutations in breast cancer, the codon-bias patterns resulting from the ssDNA target
specificities of cytidine deaminases of the AID/APOBEC family were analyzed. The data
indicate that codon context strongly influences the likely location of mutations at
motifs for AID/APOBEC1/APOBEC3G, and at WA sites. An unexpected finding is a highly significant preference for transitions of
cytosine to occur at the first nucleotide position and for transitions of guanosine
to occur at the second nucleotide position in the mutated codon (read 3′ to 5′). Thus,
the mechanisms involved appear to be sensitive to codon reading frames and to have
an intrinsic ability to differentiate between the cytosines on the nontranscribed
strand and those on the transcribed strand in the context of an open “transcription
bubble.”
Keywords
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Article info
Publication history
Published online: July 22, 2013
Accepted:
May 10,
2013
Received in revised form:
May 10,
2013
Received:
February 25,
2013
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
