Base flipping is the phenomenon whereby a base in normal B-DNA is swun
g completely out of the helix into an extrahelical position, It was di
scovered in 1994 when the first co-crystal structure was reported for
a cytosine-5 DNA methyltransferase binding to DNA, Since then it has b
een shown to occur in many systems where enzymes need access to a DNA
base to perform chemistry on it, Many DNA glycosylases that remove abn
ormal bases from DNA use this mechanism. This review describes systems
known to use base flipping as well as many systems where it is likely
to occur but has not yet been rigorously demonstrated. The mechanism
and evolution of base flipping are also discussed.