Nucleic Acids Research, 2002, Vol. 30, No. 16 3583-3591
© 2002 Oxford University Press
Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus
Laboratory of Molecular Gerontology, Box 1, National Institute on Aging, IRP, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA and 1 Lineberger Comprehensive Cancer Center, Campus Box 7295, Mason Farm Road, Department of Biochemistry and Biophysics and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599-7295, USA
*To whom correspondence should be addressed. Tel: +1 410 558 8223; Fax: +1 410 558 8157; Email: vbohr{at}nih.gov
The human Werner syndrome protein, WRN, is a member of the RecQ helicase family and contains 3'
5' helicase and 3'5' exonuclease activities. Recently, we showed that the exonuclease activity of WRN is greatly stimulated by the human Ku heterodimer protein. We have now mapped this interaction physically and functionally. The Ku70 subunit specifically interacts with the N-terminus (amino acids 1–368) of WRN, while the Ku80 subunit interacts with its C-terminus (amino acids 940– 1432). Binding between Ku70 and the N-terminus of WRN (amino acids 1–368) is sufficient for stimulation of WRN exonuclease activity. A mutant Ku heterodimer of full-length Ku80 and truncated Ku70 (amino acids 430–542) interacts with C-WRN but not with N-WRN and cannot stimulate WRN exonuclease activity. This emphasizes the functional significance of the interaction between the N-terminus of WRN and Ku70. The interaction between Ku80 and the C-terminus of WRN may modulate some other, as yet unknown, function. The strong interaction between Ku and WRN suggests that these two proteins function together in one or more pathways of DNA metabolism.
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