There are two major apurinic/apyrimidinic (AP) endonuclease/3'-diesterase families designated after the Escherichia coli proteins exonuclease III (ExoIII) and endonuclease IV (EndoIV). These repair proteins function to excise mutagenic and cytotoxic AP sites or 3'-phosphate/phosphoglycolate groups from DNA. In mammals, the predominant repair endonuclease is Ape1, a homolog of ExoIII, whereas a mammalian homolog to EndoIV has not been identified to date. We have identified a human protein termed Ape2 that represents a subclass of the ExoIII family (exhibiting highest similarity to the Saccharomyces cerevisiae ETH1/APN2 gene product) and maintains many of the essential functional residues of the ExoIII-like proteins. The human protein is 518 amino acids with a predicted molecular mass of 57.3 kDa and a pI of 8.65. Unlike Ape1, this protein exhibited only weak ability to complement the repair defects of AP endonuclease/3'-repair-defective bacteria and yeast. Similarly, a weak, but specific, DNA-binding and incision activity for abasic site-containing substrates was observed with partially purified Ape2 protein. APE2 is located on the X chromosome at position p11.21 and consists of six exons. The transcript for APE2 is ubiquitously expressed, suggesting an important function for the encoded protein. An Ape2 green fluorescent fusion protein localized predominantly to the nucleus of HeLa cells, indicating a nuclear function; this localization was dependent on the C-terminal domain. We discuss our results in the context of the evolutionary conservation of the AP endonuclease families and their divergent activities and biological contributions.

• PMID: 11152564
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Journal Article | Research Support, U.S. Gov't, Non-P.H.S. | Research Support, U.S. Gov't, P.H.S.

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Hadi MZ, Wilson DM

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