Cellular DNA is spontaneously and continuously damaged by environmental and
internal factors such as X-rays, UV light and agents such as the antitumor
drugs bleomycin and neocarzinostatin or those that generate oxygen radicals.
Apurinic/apyrimidinic (AP) sites form both spontaneously and as highly
cytotoxic intermediates in the removal of the damaged base by the base
excision repair (BER) pathway. DNA repair at the AP sites is initiated by
specific endonuclease cleavage of the phosphodiester backbone. Such
endonucleases are also generally capable of removing blocking groups from the
3'terminus of DNA strand breaks.
AP endonucleases can be classified into two families on the basis of sequence
similarity and structure (cf. family 1 <PDOC00598>). What we call family 2
groups the enzymes listed below [1,2].
Bacterial endonuclease IV (gene nfo) (EC 220.127.116.11).
Fungal and Caenorhabditis elegans apurinic endonuclase APN1 (EC 18.104.22.168).
APN1 and nfo have been shown to be transition metalloproteins that bind three
zinc ions [3,4]. The metal-binding sites have been determined from the 3D-structure of Escherichia coli nfo [4,6,7], which shows an α/β-barrel
fold (see <PDB:1QTW; A>) similar to that of other divalent metal-dependent TIM
barrel enzymes (see <PDOC00155>), such as xylose isomerase (see <PDOC00156>).
We developed three signature patterns for this family of enzymes. The patterns
are based on regions that contain conserved residues involved in zinc-binding.
We also developed a profile that covers the entire AP endonuclease family 2
February 2009 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
Popoff S.C., Spira A.I., Johnson A.W., Demple B.
Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV.
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