A conserved and species-specific functional interaction between the Werner syndrome-like exonuclease atWEX and the Ku heterodimer in Arabidopsis.
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.
Li
Baomin
B
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, LA, USA.
Conway
Nathan
N
Navarro
Sonia
S
Comai
Luca
L
Comai
Lucio
L
D000595:Amino Acid Sequence; D034961:Antigens, Nuclear / Q000378:metabolism*; D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D005092:Exonucleases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D000071657:Werner Syndrome Helicase
D034961:Antigens, Nuclear; D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; D005090:Exodeoxyribonucleases; D005092:Exonucleases; C507181:Werner-like exonuclease, Arabidopsis; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen