A conserved and species-specific functional interaction between the Werner syndrome-like exonuclease atWEX and the Ku heterodimer in Arabidopsis

摘要

Werner syndrome is associated with mutations in the DNA helicase RecQ3 [a.k.a. Homo sapiens (hs)WRN]. The function of hsWRN is unknown although biochemical studies suggest a role in DNA ends stability and repair. Unlike other RecQ family members, hsWRN possesses an N-terminal domain with exonuclease activity, which is stimulated by interaction with the Ku heterodimer. While this interaction is intriguing, we do not know whether it is important for hsWRN function. Although flies, worms, fungi and plants do not have RecQ-like (RQL) helicases with an intrinsic exonuclease activity, they possess proteins having domains homologous to the hsWRN exonuclease. The genome of Arabidopsis thaliana (at) encodes multiple RQL and a single protein with homology to the WRN exonuclease domain, atWEX (Werner-like Exonuclease). Here we show that atWEX has properties that are similar to hsWRN. atWEX binds to and is stimulated by atKu. Interestingly, stimulation by Ku is species-specific, as hsKu does not stimulate atWEX exonuclease activity. Likewise, atKu fails to enhance the exonuclease activity of hsWRN. Thus, in spite of the differences in structural organization, the functional interaction between WRN-like exonucleases and Ku has been preserved through evolutionary radiation of species, emphasizing the importance of this interaction in cell function.