A new Caenorhabditis elegans apurinic/apyrimidinic (AP) endonuclease engaged in rescue from replication stress-induced arrest

Apurinic/apyrimidinic sites are one of the most frequent spontaneous lesions in DNA. Evolutionarily conserved AP endonucleases (ExoIII and EndoIV families) incise the DNA backbone 5' to the AP site and the cleaved AP sites are subsequently repaired by the base excision repair machinery. AP endonucleases additionally exhibit 3'-5' exonuclease activity. Novel AP endonucleases that are not member of AP endonuclease families keep being reported and exhibit 3'-5' exonuclease activity and other important DNA processing. Interestingly, human and mouse WRN helicases contain a 3'-5' exonuclease domain, but the precise functional roles of the exonuclease activity in vivo remain unclear. We searched for WRN-like exonuclease proteins in the Caenorhabditis elegans database and found a new gene, zk1098.3, which shows a high similarity to human EXD3. Here, we assigned zk1098.3 to exd3-1. We cloned exd3-1 from an ORF clone and purified the recombinant EXD3-1 protein. We found that EXD3-1 displays incision at AP sites and exonucleolytic digestion on the nicked AP site and that EXD3-1 is involved in recovery from replication stress-induced cell cycle arrest. This work suggests that EXD3-1 either plays a role in base excision repair, although the extent of this repair remains to be determined, or has a specialized DNA damage response function.