InterPro: IPR018246 AP endonuclease, family 2, zinc binding site

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 can form spontaneously or 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 based on sequence similarity. Family 2 groups the enzymes listed below [1, 2].

• Bacterial endonuclease IV (EC:3.1.21.2).
• Mycobacterium leprae probable endonuclease [3].
• Saccharomyces cerevisiae (Baker's yeast) apurinic endonuclease APN1 (EC:4.2.99.18).
• Caenorhabditis elegans hypothetical protein APN-1 or T05H10.2.

APN1 and endonuclease IV have been shown to be transition metalloproteins that bind three zinc ions [4, 5]. The metal-binding sites have been determined from the 3D-structure of Escherichia coli endonuclease IV [5, 6, 7], which shows an alpha/beta-barrel fold similar to that of other divalent metal-dependent TIM barrel enzymes, such as xylose isomerase.