A new Caenorhabditis elegans AP endonuclease engaged in rescue from replication stress-induced arrest

Abstract

Apurinic/apyrimidinic (AP) sites are one of the most frequent spontaneous lesions in DNA. They are highly mutagenic and lethal lesions that can inhibit transcription and DNA replication. AP sites are primarily repaired by the base excision repair (BER) pathway which is initiated by one of the two AP endonucleases. Organisms encode for evolutionarily conserved repair machinery, including specific AP endonuclease which incises the DNA backbone 5′ to the AP site to undergo further DNA repair synthesis. We report on a new protein (EXD-3) from Caenorhabditis elegans, a putative exonuclease containing a domain homologus to human EXD3 and human Werner syndrome RNaseD, possesses endo- and exonuclease activities against abasic site. exd-3 mutants are defected in recovery from replication stress-induced cell cycle arrest and the formation of EXD-3 foci is induced by various treatments that produce double-strand breaks. Thus, EXD-3 enables to perform recognition and incision at AP sites, and further restoration (repair) of replication stress-induced damage.