Published online 7 December 2005
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A conserved and species-specific functional interaction between the Werner syndrome-like exonuclease atWEX and the Ku heterodimer in Arabidopsis
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California LA, USA 1Department of Biology, University of Washington Seattle, WA, USA
*To whom correspondence should be addressed. Tel: +1 323 442 3950; Fax: +1 323 442 2764; Email: comai{at}usc.edu
Received August 26, 2005. Revised November 10, 2005. Accepted November 10, 2005.
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.
Correspondence may also be addressed to Luca Comai. Tel: +1 206 543 4841; Fax: +1 206 685 1728; Email: comai{at}u.washington.edu
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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