The Tenacious Recognition of Yeast Telomere Sequence by Cdc13 is Fully Exerted by a Single OB-fold Domain
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Date
2013-09
Authors
Lewis, Karen A.
Pfaff, Danielle A.
Earley, Jennifer N.
Altschuler, Sarah E.
Wuttke, Deborah S.
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
Cdc13, the telomere end-binding protein from Saccharomyces cerevisiae, is a multidomain protein that specifically binds telomeric single-stranded DNA (ssDNA) with exquisitely high affinity to coordinate telomere maintenance. Recent structural and genetic data have led to the proposal that Cdc13 is the paralog of RPA70 within a telomere-specific RPA complex. Our understanding of Cdc13 structure and biochemistry has been largely restricted to studies of individual domains, precluding analysis of how each domain influences the activity of the others. To better facilitate a comparison to RPA70, we evaluated the ssDNA binding of full-length S. cerevisiae Cdc13 to its minimal substrate, Tel11. We found that, unlike RPA70 and the other known telomere end-binding proteins, the core Cdc13 ssDNA-binding activity is wholly contained within a single tight-binding oligosaccharide/oligonucleotide/oligopeptide binding (OB)-fold. Because two OB-folds are implicated in dimerization, we also evaluated the relationship between dimerization and ssDNA-binding activity and found that the two activities are independent. We also find that Cdc13 binding exhibits positive cooperativity that is independent of dimerization. This study reveals that, while Cdc13 and RPA70 share similar domain topologies, the corresponding domains have evolved different and specialized functions.
Description
Keywords
yeast telomere sequence, Cdc13, OB-fold domain, Chemistry and Biochemistry
Citation
Lewis, K. A., Pfaff, D. A., Earley, J. N., Altschuler, S. E., & Wuttke, D. S. (2013). The tenacious recognition of yeast telomere sequence by Cdc13 is fully exerted by a single OB-fold domain. Nucleic Acids Research, 42(1), pp. 475-484.
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© 2013 The Author(s).
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This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.