Structure and function of the phosphothreonine-specific FHA domain

Science Signaling

Volumn 1, Issue 51, 2008, Pages

  Mahajan, Anjali ^a   Yuan, Chunhua ^a   Lee, Hyun ^a,b   Chen, Eric S W ^b,c,d   Wu, Pei Yu ^d   Tsai, Ming Daw ^a,b,c,d  

^a OHIO STATE UNIVERSITY   (United States)

^b GENOMICS RESEARCH CENTER   (Taiwan)

^c NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^d INSTITUTE OF BIOLOGICAL CHEMISTRY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

FORKHEAD TRANSCRIPTION FACTOR; PHOSPHOTHREONINE;

BINDING SITE; CHEMISTRY; METABOLISM; PROTEIN TERTIARY STRUCTURE; REVIEW;

BINDING SITES; FORKHEAD TRANSCRIPTION FACTORS; PHOSPHOTHREONINE; PROTEIN STRUCTURE, TERTIARY;

EID: 58749117443     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.151re12     Document Type: Review

References (135)

1. K. Hofmann, P. Bucher, The FHA domain: A putative nuclear signalling domain found in protein kinases and transcription factors. Trends Biochem. Sci. 20, 347-349 (1995).
2. M. Toyota, Y. Sasaki, A. Satoh, K. Ogi, T. Kikuchi, H. Suzuki, H. Mita, N. Tanaka, F. Itoh, J. P. Issa, K. W. Jair, K. E. Schuebel, K. Imai, T. Tokino, Epigenetic inactivation of CHFR in human tumors. Proc. Natl. Acad. Sci. U.S.A. 100, 7818-7823 (2003).
3. C. K. Ea, L. Sun, J. Inoue, Z. J. Chen, TIFA activates I|B kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6. Proc. Natl. Acad. Sci. U.S.A. 101, 15318-15323 (2004).
4. N. Uhrhammer, J. O. Bay, S. Gosse-Brun, F. Kwiatkowski, P. Rio, A. Daver, Y. J. Bignon, Allelic imbalance at NBS1 is frequent in both proximal and distal colorectal carcinoma. Oncol. Rep. 7, 427-431 (2000).
5. D. Durocher, S. P. Jackson, The FHA domain. FEBS Lett. 513, 58-66 (2002).
6. A. Hammet, B. L. Pike, C. J. McNees, L. A. Conlan, N. Tenis, J. Heierhorst, FHA domains as phospho-Threonine binding modules in cell signaling. IUBMB Life 55, 23-27 (2003).
7. H. Liao, I. J. Byeon, M. D. Tsai, Structure and function of a new phosphopeptide-binding domain containing the FHA2 of Rad53. J. Mol. Biol. 294, 1041-1049 (1999).
8. A. Hammet, B. L. Pike, K. I. Mitchelhill, T. Teh, B. Kobe, C. M. House, B. E. Kemp, J. Heierhorst, FHA domain boundaries of the Dun1p and Rad53p cell cycle checkpoint kinases. FEBS Lett. 471, 141-146 (2000).
9. G. I. Lee, Z. Ding, J. C. Walker, S. R. Van Doren, NMR structure of the forkhead-Associated domain from the Arabidopsis receptor kinase-Associated protein phosphatase. Proc. Natl. Acad. Sci. U.S.A. 100, 11261-11266 (2003).
10. D. Durocher, I. A. Taylor, D. Sarbassova, L. F. Haire, S. L. Westcott, S. P. Jackson, S. J. Smerdon, M. B. Yaffe, The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms. Mol. Cell 6, 1169-1182 (2000).
11. H. Liao, C. Yuan, M. I. Su, S. Yongkiettrakul, D. Qin, H. Li, I. J. Byeon, D. Pei, M. D. Tsai, Structure of the FHA1 domain of yeast Rad53 and identification of binding sites for both FHA1 and its target protein Rad9. J. Mol. Biol. 304, 941-951 (2000).
12. J. Li, B. L. Williams, L. F. Haire, M. Goldberg, E. Wilker, D. Durocher, M. B. Yaffe, S. P. Jackson, S. J. Smerdon, Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2. Mol. Cell 9, 1045-1054 (2002).
13. N. K. Bernstein, R. S. Williams, M. L. Rakovszky, D. Cui, R. Green, F. Karimi-Busheri, R. S. Mani, S. Galicia, C. A. Koch, C. E. Cass, D. Durocher, M. Weinfeld, J. N. Glover, The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase. Mol. Cell 17, 657-670 (2005).
14. E. S. Stavridi, Y. Huyen, I. R. Loreto, D. M. Scolnick, T. D. Halazonetis, N. P. Pavletich, P. D. Jeffrey, Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein and its complex with tungstate. Structure 10, 891-899 (2002).
15. X. Xu, L. M. Tsvetkov, D. F. Stern, Chk2 activation and phosphorylation-dependent oligomerization. Mol. Cell. Biol. 22, 4419-4432 (2002).
16. C. S. Gilbert, C. M. Green, N. F. Lowndes, Budding yeast Rad9 is an ATP-dependent Rad53 activating machine. Mol. Cell 8, 129-136 (2001).
17. J. Y. Ahn, X. Li, H. L. Davis, C. E. Canman, Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-Associated domain. J. Biol. Chem. 277, 19389-19395 (2002).
18. G. Wu, Y.-G. Chen, B. Ozdamar, C. A. Gyuricza, P. A. Chong, J. L. Wrana, J. Massagué, Y. Shi, Structural basis of Smad2 recognition by the Smad anchor for receptor activation. Science 287, 92-97 (2000).
19. M. Huse, T. W. Muir, L. Xu, Y.-G. Chen, J. Kuriyan, J. Massagu, T. G. F. The, β Receptor activation process: An inhibitor-To substratebinding switch. Mol. Cell 8, 671-682 (2001).
20. S. Zhou, S. E. Shoelson, M. Chaudhuri, G. Gish, T. Pawson, W. G. Haser, F. King, T. Roberts, S. Ratnofsky, R. J. Lechleider, B. G. Neel, R. B. Birge, J. E. Fajardo, M. M. Chou, H. Hanafusa, B. Schaffhausen, L. C. Cantley, SH2 domains recognize specific phosphopeptide sequences. Cell 72, 767-778 (1993).
21. M. B. Yaffe, S. J. Smerdon, The use of in vitro peptide-library screens in the analysis of phosphoserine/ threonine-binding domain structure and function. Annu. Rev. Biophys. Biomol. Struct. 33, 225-244 (2004).
22. D. Durocher, J. Henckel, A. R. Fersht, S. P. Jackson, The FHA domain is a modular phosphopeptide recognition motif. Mol. Cell 4, 387-394 (1999).
23. Z. Sun, J. Hsiao, D. S. Fay, D. F. Stern, Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science 281, 272-274 (1998).
24. J. M. Stone, M. A. Collinge, R. D. Smith, M. A. Horn, J. C. Walker, Interaction of a protein phosphatase with an Arabidopsis serine-Threonine receptor kinase. Science 266, 793-795 (1994).
25. J. Li, G. P. Smith, J. C. Walker, Kinase interaction domain of kinase-Associated protein phosphatase, a phosphoprotein-binding domain. Proc. Natl. Acad. Sci. U.S.A. 96, 7821-7826 (1999).
26. P. Wang, I. J. Byeon, H. Liao, K. D. Beebe, S. Yongkiettrakul, D. Pei, M. D. Tsai, II, Structure and specificity of the interaction between the FHA2 domain of rad53 and phosphotyrosyl peptides. J. Mol. Biol. 302, 927-940 (2000).
27. J. Li, G. I. Lee, S. R. Van Doren, J. C. Walker, The FHA domain mediates phosphoprotein interactions. J. Cell Sci. 113, 4143-4149 (2000).
28. Z. Ding, H. Wang, X. Liang, E. R. Morris, F. Gallazzi, S. Pandit, J. Skolnick, J. C. Walker, S. R. Van Doren, Phosphoprotein and phosphopeptide interactions with the FHA domain from Arabidopsis kinase-Associated protein phosphatase. Biochemistry 46, 2684-2696 (2007).
29. M. S. Huen, R. Grant, I. Manke, K. Minn, X. Yu, M. B. Yaffe, J. Chen, RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131, 901-914 (2007).
30. D. Qin, H. Lee, C. Yuan, Y. Ju, M. D. Tsai, Identification of potential binding sites for the FHA domain of human Chk2 by in vitro binding studies. Biochem. Biophys. Res. Commun. 311, 803-808 (2003).
31. C. Yuan, S. Yongkiettrakul, I. J. Byeon, S. Zhou, M. D. Tsai, Solution structures of two FHA1-phosphothreonine peptide complexes provide insight into the structural basis of the ligand specificity of FHA1 from yeast Rad53. J. Mol. Biol. 314, 563-575 (2001).
32. H. Lee, C. Yuan, A. Hammet, A. Mahajan, E. S. Chen, M. R. Wu, M. I. Su, J. Heierhorst, M. D. Tsai, Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade. Mol. Cell 30, 767-778 (2008).
33. I. J. Byeon, H. Li, H. Song, A. M. Gronenborn, M. D. Tsai, Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67. Nat. Struct. Mol. Biol. 12, 987-993 (2005).
34. H. Kumeta, K. Ogura, S. Adachi, Y. Fujioka, N. Tanuma, K. Kikuchi, F. Inagaki, The NMR structure of the NIPP1 FHA domain. J. Biomol. NMR 40, 219-224 (2008).
35. I. J. Byeon, S. Yongkiettrakul, M. D. Tsai, Solution structure of the yeast Rad53 FHA2 complexed with a phosphothreonine peptide pTXXL: Comparison with the structures of FHA2-pYXL and FHA1-pTXXD complexes. J. Mol. Biol. 314, 577-588 (2001).
36. Z. Ding, G. I. Lee, X. Liang, F. Gallazzi, A. Arunima, S. R. Van Doren, PhosphoThr peptide binding globally rigidifies much of the FHA domain from Arabidopsis receptor kinase-Associated protein phosphatase. Biochemistry 44, 10119-10134 (2005).
37. J. Gerdes, U. Schwab, H. Lemke, H. Stein, Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int. J. Cancer 31, 13-20 (1983).
38. Z. Zhou, S. J. Elledge, DUN1 encodes a protein kinase that controls the DNA damage response in yeast. Cell 75, 1119-1127 (1993).
39. H. Li, I. J. Byeon, Y. Ju, M. D. Tsai, Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal unique recognition sites and new views to the structural basis of FHA domain functions. J. Mol. Biol. 335, 371-381 (2004).
40. S. Yongkiettrakul, I. J. Byeon, M. D. Tsai, The ligand specificity of yeast Rad53 FHA domains at the +3 position is determined by nonconserved residues. Biochemistry 43, 3862-3869 (2004).
41. S. Miyamoto, P. A. Kollman, What determines the strength of noncovalent association of ligands to proteins in aqueous solution? Proc. Natl. Acad. Sci. U.S.A. 90, 8402-8406 (1993).
42. S. Miyamoto, P. A. Kollman, Absolute and relative binding free energy calculations of the interaction of biotin and its analogs with streptavidin using molecular dynamics/free energy perturbation approaches. Proteins 16, 226-245 (1993).
43. P. Y. Huang, R. G. Carbonell, Affinity chromatographic screening of soluble combinatorial peptide libraries. Biotechnol. Bioeng. 63, 633-641 (1999).
44. G. Guillemain, E. Ma, S. Mauger, S. Miron, R. Thai, R. Guerois, F. Ochsenbein, M. C. Marsolier-Kergoat, Mechanisms of checkpoint kinase Rad53 inactivation after a double-strand break in Saccharomyces cerevisiae. Mol. Cell. Biol. 27, 3378-3389 (2007).
45. Y. Xu, M. Davenport, T. J. Kelly, Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast. Genes Dev. 20, 990-1003 (2006).
46. Z. Lou, K. Minter-Dykhouse, X. Wu, J. Chen, MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature 421, 957-961 (2003).
47. M. F. Schwartz, J. K. Duong, Z. Sun, J. S. Morrow, D. Pradhan, D. F. Stern, Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Mol. Cell 9, 1055-1065 (2002).
48. C. Leroy, S. E. Lee, M. B. Vaze, F. Ochsenbien, R. Guerois, J. E. Haber, M.-C. Marsolier-Kergoat, PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a doublestrand break. Mol. Cell 11, 827-835 (2003).
49. B. L. Pike, S. Yongkiettrakul, M. D. Tsai, J. Heierhorst, Mdt1, a novel Rad53 FHA1 domaininteracting protein, modulates DNA damage tolerance and G2/M cell cycle progression in Saccharomyces cerevisiae. Mol. Cell. Biol. 24, 2779-2788 (2004).
50. A. Mahajan, C. Yuan, B. L. Pike, J. Heierhorst, C. F. Chang, M. D. Tsai, FHA domain-ligand interactions: Importance of integrating chemical and biological approaches. J. Am. Chem. Soc. 127, 14572-14573 (2005).
51. K. Tanaka, P. Russell, Cds1 phosphorylation by Rad3-Rad26 kinase is mediated by forkheadassociated domain interaction with Mrc1. J. Biol. Chem. 279, 32079-32086 (2004).
52. K. Tanaka, M. N. Boddy, X.-B. Chen, C. H. McGowan, P. Russell, Threonine-11, phosphorylated by Rad3 and ATM in vitro, is required for activation of fission yeast checkpoint kinase Cds1. Mol. Cell. Biol. 21, 3398-3404 (2001).
53. L. J. Alderwick, V. Molle, L. Kremer, A. J. Cozzone, T. R. Dafforn, G. S. Besra, K. Futterer, Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobac-Terium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 103, 2558-2563 (2006).
54. N. Jia-Lin Ma, D. F. Stern, Regulation of the Rad53 protein kinase in signal amplification by oligomer assembly and disassembly. Cell Cycle 7, 808-817 (2008).
55. S.-J. Lee, M. F. Schwartz, J. K. Duong, D. F. Stern, Rad53 phosphorylation site clusters are important for Rad53 regulation and signaling. Mol. Cell. Biol. 23, 6300-6314 (2003).
56. T. Scholzen, J. Gerdes, The Ki-67 protein: From the known and the unknown. J. Cell. Physiol. 182, 311-322 (2000).
57. M. Takagi, Y. Matsuoka, T. Kurihara, Y. Yoneda, Chmadrin: A novel Ki-67 antigen-related perichromosomal protein possibly implicated in higher order chromatin structure. J. Cell Sci. 112, 2463-2472 (1999).
58. M. Takagi, M. Sueishi, T. Saiwaki, A. Kametaka, Y. Yoneda, A novel nucleolar protein, NIFK, interacts with the forkhead associated domain of Ki-67 antigen in mitosis. J. Biol. Chem. 276, 25386-25391 (2001).
59. M. Sueishi, M. Takagi, Y. Yoneda, The forkheadassociated domain of Ki-67 antigen interacts with the novel kinesin-like protein Hklp2. J. Biol. Chem. 275, 28888-28892 (2000).
60. J. C. Obenauer, L. C. Cantley, M. B. Yaffe, Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res. 31, 3635-3641 (2003).
61. D. Bridges, G. B. Moorhead, 14-3-3 proteins: A number of functions for a numbered protein. Sci. STKE 2005, re10 (2005).
62. J. R. Engen, T. E. Wales, J. M. Hochrein, M. A. Meyn, 3rd, S. Banu Ozkan, I. Bahar, T. E. Smithgall, Structure and dynamic regulation of Src-family kinases. Cell. Mol. Life Sci. 65, 3058-3073 (2008).
63. A. Zarrinpar, R. P. Bhattacharyya, W. A. Lim, The structure and function of proline recognition domains. Sci. STKE 2003, re8 (2003).
64. J. Bartek, J. Falck, J. Lukas, Chk2 kinase -A busy messenger. Nat. Rev. Mol. Cell Biol. 2, 877-886 (2001).
65. J.-Y. Ahn, J. K. Schwarz, H. Piwnica-Worms, C. E. Canman, Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res. 60, 5934-5936 (2000).
66. M. J. Henderson, M. A. Munoz, D. N. Saunders, J. L. Clancy, A. J. Russell, B. Williams, D. Pappin, K. K. Khanna, S. P. Jackson, R. L. Sutherland, C. K. W. Watts, EDD mediates DNA damage-induced activation of CHK2. J. Biol. Chem. 281, 39990-40000 (2006).
67. D. W. Bell, J. M. Varley, T. E. Szydlo, D. H. Kang, D. C. R. Wahrer, K. E. Shannon, M. Lubratovich, S. J. Verselis, K. J. Isselbacher, J. F. Fraumeni, J. M. Birch, F. P. Li, J. E. Garber, D. A. Haber, Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286, 2528-2531 (1999).
68. N. Sodha, T. S. Mantoni, S. V. Tavtigian, R. Eeles, M. D. Garrett, Rare germ line CHEK2 variants identified in breast cancer families encode proteins that show impaired activation. Cancer Res. 66, 8966-8970 (2006).
69. S. B. Lee, S. H. Kim, D. W. Bell, D. C. R. Wahrer, T. A. Schiripo, M. M. Jorczak, D. C. Sgroi, J. E. Garber, F. P. Li, K. E. Nichols, J. M. Varley, A. K. Godwin, K. M. Shannon, E. Harlow, D. A. Haber, Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni syndrome. Cancer Res. 61, 8062-8067 (2001).
70. X. Wu, S. R. Webster, J. Chen, Characterization of tumor-Associated Chk2 mutations. J. Biol. Chem. 276, 2971-2974 (2001).
71. J. Falck, C. Lukas, M. Protopopova, J. Lukas, G. Selivanova, J. Bartek, Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway. Oncogene 20, 5503-5510 (2001).
72. J. Falck, N. Mailand, R. G. Syljuasen, J. Bartek, J. Lukas, The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410, 842-847 (2001).
73. B. Wang, S. J. Elledge, Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc. Natl. Acad. Sci. U.S.A. 104, 20759-20763 (2007).
74. N. Mailand, S. Bekker-Jensen, H. Faustrup, F. Melander, J. Bartek, C. Lukas, J. Lukas, RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887-900 (2007).
75. N. K. Kolas, J. R. Chapman, S. Nakada, J. Ylanko, R. Chahwan, F. D. Sweeney, S. Panier, M. Mendez, J. Wildenhain, T. M. Thomson, L. Pelletier, S. P. Jackson, D. Durocher, Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318, 1637-1640 (2007).
76. R. Varon, C. Vissinga, M. Platzer, K. M. Cerosaletti, K. H. Chrzanowska, K. Saar, G. Beckmann, E. Seemanov, P. R. Cooper, N. J. Nowak, M. Stumm, C. M. R. Weemaes, R. A. Gatti, R. K. Wilson, M. Digweed, A. Rosenthal, K. Sperling, P. Concannon, A. Reis, Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93, 467-476 (1998).
77. J. P. Carney, R. S. Maser, H. Olivares, E. M. Davis, M. Le Beau, J. R. Yates, L. Hays, W. F. Morgan, J. H. J. Petrini, The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: Linkage of double-strand break repair to the cellular DNA damage response. Cell 93, 477-486 (1998).
78. T. H. Stracker, J.-W. F. Theunissen, M. Morales, J. H. J. Petrini, The Mre11 complex and the metabolism of chromosome breaks: The importance of communicating and holding things together. DNA Repair (Amsterdam) 3, 845-854 (2004).
79. E. Olson, C. J. Nievera, A. Y.-L. Lee, L. Chen, X. Wu, The Mre11-Rad50-Nbs1 complex acts both upstream and downstream of ataxia telangiectasia mutated and Rad3-related protein (ATR) to regulate the S-phase checkpoint following UV treatment. J. Biol. Chem. 282, 22939-22952 (2007).
80. S. Difilippantonio, A. Celeste, O. Fernandez-Capetillo, H. T. Chen, B. Reina San Martin, F. Van Laethem, Y. P. Yang, G. V. Petukhova, M. Eckhaus, L. Feigenbaum, K. Manova, M. Kruhlak, R. D. Camerini-Otero, S. Sharan, M. Nussenzweig, A. Nussenzweig, Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models. Nat. Cell Biol. 7, 675-685 (2005).
81. J. H. Lee, T. T. Paull, ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308, 551-554 (2005).
82. A. Kinner, W. Wu, C. Staudt, G. Iliakis, H2AX in recognition and signaling of DNA doublestrand breaks in the context of chromatin. Nucleic Acids Res. 36, 5678-5694 (2008).
83. M. Stucki, J. A. Clapperton, D. Mohammad, M. B. Yaffe, S. J. Smerdon, S. P. Jackson, MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA doublestrand breaks. Cell 123, 1213-1226 (2005).
84. C. Spycher, E. S. Miller, K. Townsend, L. Pavic, N. A. Morrice, P. Janscak, G. S. Stewart, M. Stucki, Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J. Cell Biol. 181, 227-240 (2008).
85. F. Melander, S. Bekker-Jensen, J. Falck, J. Bartek, N. Mailand, J. Lukas, Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. J. Cell Biol. 181, 213-226 (2008).
86. C. Xu, L. Wu, G. Cui, M. V. Botuyan, J. Chen, G. Mer, Structure of a second BRCT domain identified in the Nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites. J. Mol. Biol. 381, 361-372 (2008).
87. L. Wu, K. Luo, Z. Lou, J. Chen, MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks. Proc. Natl. Acad. Sci. U.S.A. 105, 11200-11205 (2008).
88. Z. Lou, K. Minter-Dykhouse, S. Franco, M. Gostissa, M. A. Rivera, A. Celeste, J. P. Manis, J. van Deursen, A. Nussenzweig, T. T. Paull, F. W. Alt, J. Chen, MDC1 maintains genomic stability by participating in the amplification of ATMdependent DNA damage signals. Mol. Cell 21, 187-200 (2006).
89. M. Goldberg, M. Stucki, J. Falck, D. D'Amours, D. Rahman, D. Pappin, J. Bartek, S. P. Jackson, MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421, 952-956 (2003).
90. G. S. Stewart, B. Wang, C. R. Bignell, A. M. Taylor, S. J. Elledge, MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421, 961-966 (2003).
91. R. S. Williams, G. Moncalian, J. S. Williams, Y. Yamada, O. Limbo, D. S. Shin, L. M. Groocock, D. Cahill, C. Hitomi, G. Guenther, D. Moiani, J. P. Carney, P. Russell, J. A. Tainer, Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell 135, 97-109 (2008).
92. R. Kanaar, C. Wyman, DNA repair by the MRN complex: break it to make it. Cell 135, 14-16 (2008).
93. J. Buis, Y. Wu, Y. Deng, J. Leddon, G. Westfield, M. Eckersdorff, J. M. Sekiguchi, S. Chang, D. O. Ferguson, Mre11 nuclease activity has essential roles in DNA repair and genomic stability distinct from ATM activation. Cell 135, 85-96 (2008).
94. C. Chappell, L. A. Hanakahi, F. Karimi-Busheri, M. Weinfeld, S. C. West, Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining. EMBO J. 21, 2827-2832 (2002).
95. C. A. Koch, R. Agyei, S. Galicia, P. Metalnikov, P. O'Donnell, A. Starostine, M. Weinfeld, D. Durocher, Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV. EMBO J. 23, 3874-3885 (2004).
96. J. I. Loizou, S. F. El-Khamisy, A. Zlatanou, D. J. Moore, D. W. Chan, J. Qin, S. Sarno, F. Meggio, L. A. Pinna, K. W. Caldecott, The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell 117, 17-28 (2004).
97. N. Gueven, O. J. Becherel, A. W. Kijas, P. Chen, O. Howe, J. H. Rudolph, R. Gatti, H. Date, O. Onodera, G. Taucher-Scholz, M. F. Lavin, Aprataxin, a novel protein that protects against genotoxic stress. Hum. Mol. Genet. 13, 1081-1093 (2004).
98. H. Luo, D. W. Chan, T. Yang, M. Rodriguez, B. P. Chen, M. Leng, J. J. Mu, D. Chen, Z. Songyang, Y. Wang, J. Qin, A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment. Mol. Cell. Biol. 24, 8356-8365 (2004).
99. P. M. Clements, C. Breslin, E. D. Deeks, P. J. Byrd, L. Ju, P. Bieganowski, C. Brenner, M. C. Moreira, A. M. Taylor, K. W. Caldecott, The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amsterdam) 3, 1493-1502 (2004).
100. S. Kanno, H. Kuzuoka, S. Sasao, Z. Hong, L. Lan, S. Nakajima, A. Yasui, A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J. 26, 2094-2103 (2007).
101. N. Iles, S. Rulten, S. F. El-Khamisy, K. W. Caldecott, APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks. Mol. Cell. Biol. 27, 3793-3803 (2007).
102. H. Zhao, K. Tanaka, E. Nogochi, C. Nogochi, P. Russell, Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission yeast. Mol. Cell. Biol. 23, 8395-8403 (2003).
103. M. Kai, M. N. Boddy, P. Russell, T. S. F. Wang, Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress. Genes Dev. 19, 919-932 (2005).
104. J. B. Allen, Z. Zhou, W. Siede, E. C. Friedberg, S. J. Elledge, The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damageinduced transcription in yeast. Genes Dev. 8, 2401-2415 (1994).
105. T. A. Weinert, G. L. Kiser, L. H. Hartwell, Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev. 8, 652-665 (1994).
106. K. Shirahige, Y. Hori, K. Shiraishi, M. Yamashita, K. Takahashi, C. Obuse, T. Tsurimoto, H. Yoshikawa, Regulation of DNA-replication origins during cell-cycle progression. Nature 395, 618-621 (1998).
107. S. Kim, T. A. Weinert, Characterization of the checkpoint gene RAD53/MEC2 in Saccharomyces cerevisiae. Yeast 13, 735-745 (1997).
108. M. P. Longhese, V. Paciotti, H. Neecke, G. Lucchini, Checkpoint proteins influence telomeric silencing and length maintenance in budding yeast. Genetics 155, 1577-1591 (2000).
109. M. F. Schwartz, S. J. Lee, J. K. Duong, S. Eminaga, D. F. Stern, FHA domain-mediated DNA checkpoint regulation of Rad53. Cell Cycle 2, 384-396 (2003).
110. B. L. Pike, S. Yongkiettrakul, M.-D. Tsai, J. Heierhorst, Diverse but overlapping functions of the two forkhead-Associated (FHA) domains in Rad53 checkpoint kinase activation. J. Biol. Chem. 278, 30421-30424 (2003).
111. A. A. Alcasabas, A. J. Osborn, J. Bachant, F. Hu, P. J. Werler, K. Bousset, K. Furuya, J. F. Diffley, A. M. Carr, S. J. Elledge, Mrc1 transduces signals of DNA replication stress to activate Rad53. Nat. Cell Biol. 3, 958-965 (2001).
112. A. J. Osborn, S. J. Elledge, Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53. Genes Dev. 17, 1755-1767 (2003).
113. F. D. Sweeney, F. Yang, A. Chi, J. Shabanowitz, D. F. Hunt, D. Durocher, Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Curr. Biol. 15, 1364-1375 (2005).
114. B. L. Pike, N. Tenis, J. Heierhorst, Rad53 kinase activation-independent replication checkpoint function of the N-Terminal forkhead-Associated (FHA1) domain. J. Biol. Chem. 279, 39636-39644 (2004).
115. M. B. Smolka, S.-h. Chen, P. S. Maddox, J. M. Enserink, C. P. Albuquerque, X. X. Wei, A. Desai, R. D. Kolodner, H. Zhou, An FHA domain-mediated protein interaction network of Rad53 reveals its role in polarized cell growth. J. Cell Biol. 175, 743-753 (2006).
116. J.-L. Ma, S.-J. Lee, J. K. Duong, D. F. Stern, Activation of the checkpoint kinase Rad53 by the phosphatidyl inositol kinase-like kinase Mec1. J. Biol. Chem. 281, 3954-3963 (2006).
117. A. T. Y. Tam, B. L. Pike, J. Heierhorst, Locationspecific functions of the two forkhead-Associated domains in Rad53 checkpoint kinase signaling. Biochemistry 47, 3912-3916 (2008).
118. V. I. Bashkirov, E. V. Bashkirova, E. Haghnazari, W.-D. Heyer, Direct kinase-To-kinase signaling mediated by the FHA phosphoprotein recognition domain of the Dun1 DNA damage checkpoint kinase. Mol. Cell. Biol. 23, 1441-1452 (2003).
119. S. H. Chen, M. B. Smolka, H. Zhou, Mechanism of Dun1 activation by Rad53 phosphorylation in Saccharomyces cerevisiae. J. Biol. Chem. 282, 986-995 (2007).
120. A. Krupa, G. Preethi, N. Srinivasan, Structural modes of stabilization of permissive phosphorylation sites in protein kinases: Distinct strategies in Ser/Thr and Tyr kinases. J. Mol. Biol. 339, 1025-1039 (2004).
121. Y. Ho, A. Gruhler, A. Heilbut, G. D. Bader, L. Moore, S.-L. Adams, A. Millar, P. Taylor, K. Bennett, K. Boutilier, L. Yang, C. Wolting, I. Donaldson, S. Schandorff, J. Shewnarane, M. Vo, J. Taggart, M. Goudreault, B. Muskat, C. Alfarano, D. Dewar, Z. Lin, K. Michalickova, A. R. Willems, H. Sassi, P. A. Nielsen, K. J. Rasmussen, J. R. Andersen, L. E. Johansen, L. H. Hansen, H. Jespersen, A. Podtelejnikov, E. Nielsen, J. Crawford, V. Poulsen, B. D. Sorensen, J. Matthiesen, R. C. Hendrickson, F. Gleeson, T. Pawson, M. F. Moran, D. Durocher, M. Mann, C. W. V. Hogue, D. Figeys, M. Tyers, Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180-183 (2002).
122. J. Li, G. P. Smith, J. C. Walker, Kinase interaction domain of kinase-Associated protein phosphatase, a phosphoprotein-binding domain. Proc. Natl. Acad. Sci. U.S.A. 96, 7821-7826 (1999).
123. J. M. Stone, A. E. Trotochaud, J. C. Walker, S. E. Clark, Control of meristem development by CLAVATA1 receptor kinase and kinase-Associated protein phosphatase interactions. Plant Physiol. 117, 1217-1225 (1998).
124. E. R. Morris, D. Chevalier, J. C. Walker, DAWDLE, a forkhead-Associated domain gene, regulates multiple aspects of plant development. Plant Physiol. 141, 932-941 (2006).
125. B. Yu, L. Bi, B. Zheng, L. Ji, D. Chevalier, M. Agarwal, V. Ramachandran, W. Li, T. Lagrange, J. C. Walker, X. Chen, The FHA domain proteins DAWDLE in Arabidopsis and SNIP1 in humans act in small RNA biogenesis. Proc. Natl. Acad. Sci. U.S.A. 105, 10073-10078 (2008).
126. M. Kim, J.-W. Ahn, K. Song, K.-H. Paek, H.-S. Pai, Forkhead-Associated domains of the tobacco NtFHA1 transcription activator and the yeast Fhl1 forkhead transcription factor are functionally conserved. J. Biol. Chem. 277, 38781-38790 (2002).
127. C. J. Bakal, J. E. Davies, No longer an exclusive club: Eukaryotic signalling domains in bacteria. Trends Cell Biol. 10, 32-38 (2000).
128. S. Inouye, R. Jain, T. Ueki, H. Nariya, C. Y. Xu, M. Y. Hsu, B. A. Fernandez-Luque, J. Munoz-Dorado, E. Farez-Vidal, M. Inouye, A large family of eukaryotic-like protein Ser/Thr kinases of Myxococcus xanthus, a developmental bacterium. Microb. Comp. Genomics 5, 103-120 (2000).
129. M. Pallen, R. Chaudhuri, A. Khan, Bacterial FHA domains: Neglected players in the phospho-Threonine signalling game? Trends Microbiol. 10, 556-563 (2002).
130. A. Telenti, W. J. Philipp, S. Sreevatsan, C. Bernasconi, K. E. Stockbauer, B. Wieles, J. M. Musser, W. R. Jacobs, Jr., The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat. Med. 3, 567-570 (1997).
131. A. E. Belanger, G. S. Besra, M. E. Ford, K. Mikusova, J. T. Belisle, P. J. Brennan, J. M. Inamine, The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc. Natl. Acad. Sci. U.S.A. 93, 11919-11924 (1996).
132. K. G. Papavinasasundaram, B. Chan, J.-H. Chung, M. J. Colston, E. O. Davis, Y. Av-Gay, Deletion of the Mycobacterium tuberculosis pknH gene confers a higher bacillary load during the chronic phase of infection in BALB/c mice. J. Bacteriol. 187, 5751-5760 (2005).
133. K. Rittinger, J. Budman, J. Xu, S. Volinia, L. C. Cantley, S. J. Smerdon, S. J. Gamblin, M. B. Yaffe, Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Mol. Cell 4, 153-166 (1999).
134. S. M. Pascal, A. U. Singer, T. Yamazaki, L. E. Kay, J. D. Forman-Kay, Structural and dynamic characterization of an SH2 domain-phosphopeptide complex by NMR approaches. Biochem. Soc. Trans. 23, 729-733 (1995).
135. M. A. Verdecia, M. E. Bowman, K. P. Lu, T. Hunter, J. P. Noel, Structural basis for phosphoserine-proline recognition by group IV WW domains. Nat. Struct. Biol. 7, 639-643 (2000).