The incorporation of ribonucleotides in DNA has attracted considerable notice in 
recent years, since the pool of ribonucleotides can exceed that of the 
deoxyribonucleotides by at least 10-20-fold, and single ribonucleotide 
incorporation by DNA polymerases appears to be a common event. Moreover 
ribonucleotides are potentially mutagenic and lead to genome instability. As a 
consequence, errantly incorporated ribonucleotides are rapidly repaired in a 
process dependent upon RNase H enzymes. On the other hand, global genomic 
nucleotide excision repair (NER) in prokaryotes and eukaryotes removes damage 
caused by covalent modifications that typically distort and destabilize DNA 
through the production of lesions derived from bulky chemical carcinogens, such 
as polycyclic aromatic hydrocarbon metabolites, or via crosslinking. However, a 
recent study challenges this lesion-recognition paradigm. The work of Vaisman et 
al. (2013) [34] reveals that even a single ribonucleotide embedded in a 
deoxyribonucleotide duplex is recognized by the bacterial NER machinery in 
vitro. In their report, the authors show that spontaneous mutagenesis promoted 
by a steric-gate pol V mutant increases in uvrA, uvrB, or uvrC strains lacking 
rnhB (encoding RNase HII) and to a greater extent in an NER-deficient strain 
lacking both RNase HI and RNase HII. Using purified UvrA, UvrB, and UvrC 
proteins in in vitro assays they show that despite causing little distortion, a 
single ribonucleotide embedded in a DNA duplex is recognized and doubly-incised 
by the NER complex. We present the hypothesis to explain the recognition and/or 
verification of this small lesion, that the critical 2'-OH of the ribonucleotide 
- with its unique electrostatic and hydrogen bonding properties - may act as a 
signal through interactions with amino acid residues of the prokaryotic NER 
complex that are not possible with DNA. Such a mechanism might also be relevant 
if it were demonstrated that the eukaryotic NER machinery likewise incises an 
embedded ribonucleotide in DNA.