dna base flipping, or nucleotide flipping, is a mechanism in which a single nucleotide base, or nucleobase, is rotated outside the nucleic acid double helix. this occurs when a nucleic acid-processing enzyme needs access to the base to perform work on it, such as its excision for replacement with another base during dna repair. it was first observed in 1994 using x-ray crystallography in a methyltransferase enzyme catalyzing methylation of a cytosine base in dna. since then, it has been shown to be used by different enzymes in many biological processes such as dna methylation, various dna repair mechanisms, and dna replication. it can also occur in rna double helices or in the dna:rna intermediates formed during rna transcription.