Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions

作者: Albert Ribes-Zamora , Ivana Mihalek , Olivier Lichtarge , Alison A Bertuch

DOI: 10.1038/NSMB1214

关键词:

摘要: The Ku heterodimer, comprised of Ku70 and Ku80 subunits, is a conserved complex involved in nonhomologous end-joining (NHEJ). However, it also functions maintenance telomeres, chromosome termini normally resistant to events. To elucidate the spatial organization these functions, we rationally guided mutagenesis yeast with real-valued evolutionary trace (rvET). This revealed two ancestrally related α-helices: one on surface that required for NHEJ, second telomeric heterochromatin formation. When bound DNA end, containing NHEJ-specific helix oriented toward terminus, whereas function–specific faces inward, chromatin, when telomere. We propose 'two-face' model divergent evolution allowed Ku's dual role NHEJ telomere maintenance.

参考文章(50)
Mathew E. Sowa, Wei He, Kevin C. Slep, Michele A. Kercher, Olivier Lichtarge, Theodore G. Wensel, Prediction and confirmation of a site critical for effector regulation of RGS domain activity. Nature Structural & Molecular Biology. ,vol. 8, pp. 234- 237 ,(2001) , 10.1038/84974
Michael S. Waterman, Introduction to computational biology : Chapman & Hall. ,(1995) , 10.1007/978-1-4899-6846-3
William S.J. Valdar, Scoring residue conservation. Proteins. ,vol. 48, pp. 227- 241 ,(2002) , 10.1002/PROT.10146
Valeria Viscardi, Michela Clerici, Hugo Cartagena-Lirola, Maria Pia Longhese, Telomeres and DNA damage checkpoints. Biochimie. ,vol. 87, pp. 613- 624 ,(2005) , 10.1016/J.BIOCHI.2004.10.022
Alison A. Bertuch, Victoria Lundblad, The Ku heterodimer performs separable activities at double-strand breaks and chromosome termini. Molecular and Cellular Biology. ,vol. 23, pp. 8202- 8215 ,(2003) , 10.1128/MCB.23.22.8202-8215.2003
H.-L. Hsu, D. Gilley, E. H. Blackburn, D. J. Chen, Ku is associated with the telomere in mammals Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 12454- 12458 ,(1999) , 10.1073/PNAS.96.22.12454
Karel Riha, Michelle L. Heacock, Dorothy E. Shippen, The role of the nonhomologous end-joining DNA double-strand break repair pathway in telomere biology. Annual Review of Genetics. ,vol. 40, pp. 237- 277 ,(2006) , 10.1146/ANNUREV.GENET.39.110304.095755
Cyrus Chothia, The nature of the accessible and buried surfaces in proteins Journal of Molecular Biology. ,vol. 105, pp. 1- 12 ,(1976) , 10.1016/0022-2836(76)90191-1
Giulia B. Celli, Eros Lazzerini Denchi, Titia de Lange, Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nature Cell Biology. ,vol. 8, pp. 885- 890 ,(2006) , 10.1038/NCB1444