Chapter IV Summary
4.2 Future Perspective
In this study, I observed the roles of the IDR linker of p53 on the binding to and the sliding along DNA. In addition, I characterized the transient encounter complex, the jumping, and the hopping coupled to the 1D diffusion. I proposed that each of the characterized mechanisms might be controlled by the different conformations assumed by p53 during its binding to and sliding along DNA. I proposed that one of the four C-terminus domains of p53 interacts with DNA during the formation of transient encounter complex and that the other DNA binding domains are recruited to interact more tightly with DNA in the stable complex. I also proposed that the individual DNA binding domain of p53 hops along DNA at the higher salt concentrations, causing the acceleration of the diffusion along DNA. When all of the DNA binding domains dissociate simultaneously, p53 would dissociate away from DNA and switch to the jumping or to the 3D diffusion. I thought that the conformation assumed by p53 should be very important in determining the dynamic events in the target search and in increasing the target search efficiency of p53.
In Chapter 3, I conducted an experiment aiming at the elucidation of the relationship between the conformation and the dynamics by using the two-color single-molecule Förster resonance energy transfer (smFRET) imaging. The preliminary result indicated that the conformational changes do
the observed dynamics, however, more data and further analysis are required. For this purpose, it is desirable to prepare more samples of p53 in which dye pairs are labeled at different locations such as CT-CT as used in chapter 3, Core-CT and Core-Core. The samples would enable to piece together how the conformation of p53 changes as it binds to DNA from the transient encounter complex to the stable complex performing the 1D diffusion with different sliding modes, as previously reported by our research group, and finally to the recognition of the target site. The clarification of these events may reveal the significance of a unique structure of p53 in the target search process.
The experiments I have described thus far are under in vitro condition where only free DNA and p53 are present in the solution. In the nucleus of living cells, however, DNAs are wrapped around histone proteins to form nucleosome and folded into compact chromosomes. DBPs, including p53, are required to search for their target sequence embedded in the complex DNA structures in the presence of various other DBPs looking for their respective target sequences. Nili et al reported that p53 binding sites reside preferentially within genomic regions with relatively high nucleosome occupancy. They also showed that upon DNA damage nucleosomes are partially and reversibly displaced from the regions surrounding the p53 binding sites147. In addition, Laptenko et al. found that p53 is able to bind to nucleosomal DNA containing its p21 response element148. Furthermore, in vivo single-molecule microscopy by Mazza et al. revealed that p53 can bind to chromatins in cells
149.
While the reports above confirmed and characterized the interaction between p53 and nucleosomal DNA, the dynamic interactions involved in such events remain unclear. For example, how does single nucleosome affect p53 target search? How does a set of nucleosomes clustered together affect the dynamics of p53? One way of considering the events is that nucleosomes act as obstacles and interfere the diffusion of p53 along DNA. The jump and non-rotational coupled motions we observed in this study might be the mechanism that p53 uses in live cells to overcome such obstacles. This mechanism should be investigated further by introducing labeled nucleosomes into the DNA array and by simultaneously observing the p53 dynamics by using the two-color single-molecule imaging. It should be noted that acting as obstacles does not necessarily mean that nucleosomes will impede the target search. In fact, using coarse-grained molecular dynamics simulation, Kanada et al. proposed that nucleosome crowding may improves the target search time despite causing p53 to have lower diffusion 150. Comprehensive single-molecule investigation of p53 target search in the presence of nucleosome and other DNA binding proteins will help unveiling the dynamics of p53 target search in vivo.
References
[1] Magasanik, B. (1970) Glucose Effects: Inducer Exclusion and Repression, 189--219.
[2] Contesse, G., Crepin, M., Gros, F., Ullmann, A., and Monod, J. (1970) On the Mechanism of Catabolite Repression, 401--415.
[3] Riggs, A. D., Bourgeois, S., and Cohn, M. (1970) The lac repressor-operator interaction. 3. Kinetic studies, J Mol Biol 53, 401-417.
[4] Bresloff, J. L., and Crothers, D. M. (1975) DNA-ethidium reaction kinetics: Demonstration of direct ligand transfer between DNA binding sites, Journal of Molecular Biology 95, 103-123.
[5] Berg, O. G., Winter, R. B., and Von Hippel, P. H. (1981) Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory, Biochemistry 20, 6929-6948.
[6] Winter, R. B., Berg, O. G., and Von Hippel, P. H. (1981) Diffusion-driven mechanisms of protein translocation on nucleic acids. 3. The Escherichia coli lac repressor-operator interaction:
kinetic measurements and conclusions, Biochemistry 20, 6961-6977.
[7] Berg, O. G. (1978) On diffusion-controlled dissociation, Chemical Physics 31, 47-57.
[8] Hedglin, M., and O'Brien, P. J. (2010) Hopping enables a DNA repair glycosylase to search both strands and bypass a bound protein, ACS Chem Biol 5, 427-436.
[9] Bonnet, I., Biebricher, A., Porte, P. L., Loverdo, C., Benichou, O., Voituriez, R., Escude, C., Wende, W., Pingoud, A., and Desbiolles, P. (2008) Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA, Nucleic Acids Res 36, 4118-4127.
[10] Slutsky, M., and Mirny, L. A. (2004) Kinetics of protein-DNA interaction: Facilitated target location in sequence-dependent potential, Biophysical Journal 87, 4021--4035.
[11] Tafvizi, A., Mirny, L. A., and van Oijen, A. M. (2011) Dancing on DNA: kinetic aspects of search processes on DNA, Chemphyschem 12, 1481-1489.
[12] Lane, D. P., and Crawford, L. V. (1979) T antigen is bound to a host protein in SV40-transformed cells, Nature 278, 261-263.
[13] Linzer, D. I. H., and Levine, A. J. (1979) Characterization of a 54K Dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells, Cell 17, 43-52.
[14] Joerger, A. C., and Fersht, A. R. (2007) Structure-function-rescue: the diverse nature of common p53 cancer mutants, Oncogene 26, 2226-2242.
[15] Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., and Lane, D. P. (2009) Awakening guardian angels: drugging the p53 pathway, Nat Rev Cancer 9, 862-873.
[16] Beckerman, R., and Prives, C. (2010) Transcriptional regulation by p53, Cold Spring Harb Perspect Biol 2, a000935.
[17] Bieging, K. T., Mello, S. S., and Attardi, L. D. (2014) Unravelling mechanisms of p53-mediated tumour suppression, Nature Reviews Cancer 14, 359-370.
[18] Laptenko, O., Tong, D. R., Manfredi, J., and Prives, C. (2016) The Tail That Wags the Dog:
How the Disordered C-Terminal Domain Controls the Transcriptional Activities of the p53 Tumor-Suppressor Protein, Trends Biochem. Sci. 41, 1022-1034.
[19] Kamagata, K., Murata, A., Itoh, Y., and Takahashi, S. (2017) Characterization of facilitated diffusion of tumor suppressor p53 along DNA using single-molecule fluorescence imaging, J Photochem Photobiol C Photochem Reviews 30, 36-50.
[20] Haupt, Y., Maya, R., Kazaz, A., and Oren, M. (1997) Mdm2 promotes the rapid degradation of p53, Nature 387, 296-299.
[21] Honda, R., Tanaka, H., and Yasuda, H. (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53, FEBS Letters 420, 25-27.
[22] Vogelstein, B., Lane, D., and Levine, J. (2000) Surfing the p53 network., Nature 408, 307--310.
[23] Lane, D., and Levine, A. (2010) p53 Research : The Past Thirty Years and the Next Thirty Years p53 Research : The Past Thirty Years and, Cold Spring Harbor Perspectives in Biology 2, 1--11.
[24] Ryan, K. M., Phillips, A. C., and Vousden, K. H. (2001) Regulation and function of the p53 tumor suppressor protein, Current Opinion in Cell Biology 13, 332-337.
[25] Meek, D. W., and Anderson, C. W. (2009) Posttranslational Modification of p53: Cooperative Integrators of Function, Cold Spring Harb. Perspect. Biol. 1, a000950.
[26] Wang, Y. V., Wade, M., Wong, E., Li, Y. C., Rodewald, L. W., and Wahl, G. M. (2007) Quantitative analyses reveal the importance of regulated Hdmx degradation for P53 activation, Proc. Natl. Acad. Sci. U. S. A. 104, 12365-12370.
[27] Joerger, A. C., and Fersht, A. R. (2010) The tumor suppressor p53: from structures to drug discovery, Cold Spring Harb Perspect Biol 2, a000919.
[28] Hanel W., Marchenko N., Xu S., Xiaofeng Yu S., Weng W., and U., M. (2013) Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis, 20, 898-909.
[29] Kitayner, M., Rozenberg, H., Kessler, N., Rabinovich, D., Shaulov, L., Haran, T. E., and Shakked, Z. (2006) Structural Basis of DNA Recognition by p53 Tetramers, Molecular Cell 22, 741-753.
[30] Joerger, A. C., and Fersht, A. R. (2007) Structural biology of the tumor suppressor p53 and
[31] Malecka, K. A., Ho, W. C., and Marmorstein, R. (2009) Crystal structure of a p53 core tetramer bound to DNA, Oncogene 28, 325-333.
[32] Emamzadah, S., Tropia, L., and Halazonetis, T. D. (2011) Crystal structure of a multidomain human p53 tetramer bound to the natural CDKN1A (p21) p53-response element, Mol Cancer Res 9, 1493-1499.
[33] Weinberg, R. L., Freund, S. M., Veprintsev, D. B., Bycroft, M., and Fersht, A. R. (2004) Regulation of DNA binding of p53 by its C-terminal domain, J Mol Biol 342, 801-811.
[34] Friedler, A., Veprintsev, D. B., Freund, S. M., von Glos, K. I., and Fersht, A. R. (2005) Modulation of binding of DNA to the C-terminal domain of p53 by acetylation, Structure 13, 629-636.
[35] Marchenko, N. D., Hanel, W., Li, D., Becker, K., Reich, N., and Moll, U. M. (2010) Stress-mediated nuclear stabilization of p53 is regulated by ubiquitination and importin-alpha3 binding, Cell Death Differ 17, 255-267.
[36] Olivier, M., Eeles, R., Hollstein, M., Khan, M. A., Harris, C. C., and Hainaut, P. (2002) The IARC TP53 Database: New Online Mutation Analysis and Recommendations to Users, Human Mutation 19, 607-614.
[37] Weinberg, R. L., Veprintsev, D. B., and Fersht, A. R. (2004) Cooperative binding of tetrameric p53 to DNA, J Mol Biol 341, 1145-1159.
[38] Weinberg, R. L., Veprintsev, D. B., Bycroft, M., and Fersht, A. R. (2005) Comparative binding of p53 to its promoter and DNA recognition elements, J Mol Biol 348, 589-596.
[39] Petty, T. J., Emamzadah, S., Costantino, L., Petkova, I., Stavridi, E. S., Saven, J. G., Vauthey, E., and Halazonetis, T. D. (2011) An induced fit mechanism regulates p53 DNA binding kinetics to confer sequence specificity, EMBO J 30, 2167-2176.
[40] Murata, A., Ito, Y., Kashima, R., Kanbayashi, S., Nanatani, K., Igarashi, C., Okumura, M., Inaba, K., Tokino, T., Takahashi, S., and Kamagata, K. (2015) One-Dimensional Sliding of p53 Along DNA Is Accelerated in the Presence of Ca(2+) or Mg(2+) at Millimolar Concentrations, J Mol Biol 427, 2663-2678.
[41] Itoh, Y., Murata, A., Sakamoto, S., Nanatani, K., Wada, T., Takahashi, S., and Kamagata, K.
(2016) Activation of p53 facilitates the target search in DNA by enhancing the target recognition probability, J. Mol. Biol. 428, 2916-2930.
[42] McKinney, K., Mattia, M., Gottifredi, V., and Prives, C. (2004) p53 linear diffusion along DNA requires its C terminus, Mol. Cell 16, 413-424.
[43] Tafvizi, A., Huang, F., Leith, J. S., Fersht, A. R., Mirny, L. A., and van Oijen, A. M. (2008) Tumor suppressor p53 slides on DNA with low friction and high stability, Biophys J 95, L01-03.
[44] Tafvizi, A., Huang, F., Fersht, A. R., Mirny, L. A., and van Oijen, A. M. (2011) A single-molecule characterization of p53 search on DNA, Proc. Natl. Acad. Sci. U. S. A. 108, 563-568.
[45] Leith, J. S., Tafvizi, A., Huang, F., Uspal, W. E., Doyle, P. S., Fersht, A. R., Mirny, L. A., and van Oijen, A. M. (2012) Sequence-dependent sliding kinetics of p53, Proc Natl Acad Sci U S A 109, 16552-16557.
[46] Murata, A., Itoh, Y., Mano, E., Kanbayashi, S., Igarashi, C., Takahashi, H., Takahashi, S., and Kamagata, K. (2017) One-Dimensional Search Dynamics of Tumor Suppressor p53 Regulated by a Disordered C-Terminal Domain, Biophys. J. 112, 2301-2314.
[47] Subekti, D. R. G., Murata, A., Itoh, Y., Fukuchi, S., Takahashi, H., Kanbayashi, S., Takahashi, S., and Kamagata, K. (2017) The disordered linker in p53 participates in nonspecific binding to and one-dimensional sliding along DNA revealed by single-molecule fluorescence measurements, Biochemistry 56, 4134-4144.
[48] Itoh, Y., Murata, A., Takahashi, S., and Kamagata, K. (2018) Intrinsically disordered domain of tumor suppressor p53 facilitates target search by ultrafast transfer between different DNA strands, Nucleic Acids Res. 46, 7261-7269.
[49] Kamagata, K., Mano, E., Itoh, Y., Wakamoto, T., Kitahara, R., Kanbayashi, S., Takahashi, H., Murata, A., and Kameda, T. (2019) Rational design using sequence information only produces a peptide that binds to the intrinsically disordered region of p53, Sci. Rep. 9, 8584.
[50] Bénichou, O. L., C.Moreau, M.Voituriez, R. (2011) Intermittent search strategies, Rev. Mod.
Phys. 83, 81-129.
[51] Schmidt, H. G., Sewitz, S., Andrews, S. S., and Lipkow, K. (2014) An integrated model of transcription factor diffusion shows the importance of intersegmental transfer and quaternary protein structure for target site finding, PLoS One 9, e108575.
[52] Igarashi, C., Murata, A., Itoh, Y., Subekti, D. R. G., Takahashi, S., and Kamagata, K. (2017) DNA Garden: A Simple Method for Producing Arrays of Stretchable DNA for Single-Molecule Fluorescence Imaging of DNA Binding Proteins, Bull. Chem. Soc. Jpn. 90, 34-43.
[53] Avantaggiati, M. L., Ogryzko, V., Gardner, K., Giordano, A., Levine, A. S., and Kelly, K. (1997) Recruitment of p300/CBP in p53-dependent signal pathways, Cell 89, 1175-1184.
[54] Scolnick, D. M., Chehab, N. H., Stavridi, E. S., Lien, M. C., Caruso, L., Moran, E., Berger, S.
transcriptional coactivators of the p53 tumor suppressor protein, Cancer research 57, 3693-3696.
[55] Ohki, R., Kawase, T., Ohta, T., Ichikawa, H., and Taya, Y. (2007) Dissecting functional roles of p53 N-terminal transactivation domains by microarray expression analysis, Cancer Sci 98, 189-200.
[56] Jenkins, L. M. M., Durell, S. R., Mazur, S. J., and Appella, E. (2012) p53 N-terminal phosphorylation: a defining layer of complex regulation, Carcinogenesis 33, 1441-1449.
[57] Jayaraman, L., and Prives, C. (1999) Covalent and noncovalent modifiers of the p53 protein, Cell. Mol. Life Sci. 55, 76-87.
[58] D'Abramo, M., Besker, N., Desideri, A., Levine, A. J., Melino, G., and Chillemi, G. (2016) The p53 tetramer shows an induced-fit interaction of the C-terminal domain with the DNA-binding domain, Oncogene 35, 3272-3281.
[59] Emamzadah, S., Tropia, L., Vincenti, I., Falquet, B., and Halazonetis, T. D. (2014) Reversal of the DNA-binding-induced loop L1 conformational switch in an engineered human p53 protein, J. Mol. Biol. 426, 936-944.
[60] Melero, R., Rajagopalan, S., Lazaro, M., Joerger, A. C., Brandt, T., Veprintsev, D. B., Lasso, G., Gil, D., Scheres, S. H., Carazo, J. M., Fersht, A. R., and Valle, M. (2011) Electron microscopy studies on the quaternary structure of p53 reveal different binding modes for p53 tetramers in complex with DNA, Proc Natl Acad Sci U S A 108, 557-562.
[61] Tidow, H., Melero, R., Mylonas, E., Freund, S. M., Grossmann, J. G., Carazo, J. M., Svergun, D. I., Valle, M., and Fersht, A. R. (2007) Quaternary structures of tumor suppressor p53 and a specific p53 DNA complex, Proc. Natl. Acad. Sci. U. S. A. 104, 12324-12329.
[62] Bista, M., Freund, S. M., and Fersht, A. R. (2012) Domain-domain interactions in full-length p53 and a specific DNA complex probed by methyl NMR spectroscopy, Proc Natl Acad Sci U S A 109, 15752-15756.
[63] Chene, P. (2001) The role of tetramerization in p53 function, Oncogene 20, 2611-2617.
[64] Shaulsky, G., Goldfinger, N., Ben-Ze'ev, A., and Rotter, V. (1990) Nuclear accumulation of p53 protein is mediated by several nuclear localization signals and plays a role in tumorigenesis, Mol. Cell. Biol. 10, 6565-6577.
[65] Jayaraman, L., and Prives, C. (1995) Activation of p53 sequence-specific DNA bindingby short single strands of DNA requires the p53 C-terminus, Cell 81, 1021-1029.
[66] Gu, W., Roeder, R. G. (1997) Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain, Cell 90, 595 - 606.
[67] Yakovleva, T., Pramanik, A., Kawasaki, T., Tan-No, K., Gileva, I., Lindegren, H., Langel, U., Ekstrom, T. J., Rigler, R., Terenius, L., and Bakalkin, G. (2001) p53 Latency. C-terminal domain prevents binding of p53 core to target but not to nonspecific DNA sequences, J Biol Chem 276, 15650-15658.
[68] Hamard, P.-J., Lukin, D. J., and Manfredi, J. J. (2012) p53 Basic C Terminus Regulates p53 Functions through DNA Binding Modulation of Subset of Target Genes, Journal of Biological Chemistry 287, 22397-22407.
[69] Liang, S. H., and Clarke, M. F. (1999) A bipartite nuclear localization signal is required for p53 nuclear import regulated by a carboxyl-terminal domain, J Biol Chem 274, 32699-32703.
[70] O'Keefe, K., Li, H., and Zhang, Y. (2003) Nucleocytoplasmic Shuttling of p53 Is Essential for MDM2-Mediated Cytoplasmic Degradation but Not Ubiquitination, Molecular and Cellular Biology 23, 6396-6405.
[71] Arrowsmith, C. H. (1999) Structure and function in the p53 family, Cell Death Differ. 6, 1169-1173.
[72] Klemm, J. D., and Pabo, C. O. (1996) Oct-1 POU domain-DNA interactions: cooperative binding of isolated subdomains and effects of covalent linkage, Genes Dev. 10, 27-36.
[73] Zhou, H. X. (2001) Single-chain versus dimeric protein folding: thermodynamic and kinetic consequences of covalent linkage, J. Am. Chem. Soc. 123, 6730-6731.
[74] Zhou, H. X. (2001) The affinity-enhancing roles of flexible linkers in two-domain DNA-binding proteins, Biochemistry 40, 15069-15073.
[75] Pavletich, N. P., and Pabo, C. O. (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A, Science 252, 809-817.
[76] vanLeeuwen, H. C., Strating, M. J., Rensen, M., deLaat, W., and vanderVliet, P. C. (1997) Linker length and composition influence the flexibility of Oct-1 DNA binding, EMBO J. 16, 2043-2053.
[77] Laity, J. H., Dyson, H. J., and Wright, P. E. (2000) DNA-induced alpha-helix capping in conserved linker sequences is a determinant of binding affinity in Cys(2)-His(2) zinc fingers, J. Mol. Biol. 295, 719-727.
[78] Liu, J., Perumal, N. B., Oldfield, C. J., Su, E. W., Uversky, V. N., and Dunker, A. K. (2006) Intrinsic disorder in transcription factors, Biochemistry 45, 6873-6888.
[79] Elrod-Erickson, M., Rould, M. A., Nekludova, L., and Pabo, C. O. (1996) Zif268 protein-DNA complex refined at 1.6 A: a model system for understanding zinc finger-DNA interactions, Structure 4, 1171-1180.
[80] Xu, H. E., Rould, M. A., Xu, W., Epstein, J. A., Maas, R. L., and Pabo, C. O. (1999) Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding, Genes Dev. 13, 1263-1275.
[81] Waterman, J. L., Shenk, J. L., and Halazonetis, T. D. (1995) The dihedral symmetry of the p53 tetramerization domain mandates a conformational switch upon DNA binding, EMBO J. 14, 512-519.
[82] el-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., and Vogelstein, B. (1992) Definition of a consensus binding site for p53, Nat. Genet. 1, 45-49.
[83] Terakawa, T., and Takada, S. (2015) p53 dynamics upon response element recognition explored by molecular simulations, Sci Rep 5, 17107.
[84] Scully, K. M., Jacobson, E. M., Jepsen, K., Lunyak, V., Viadiu, H., Carriere, C., Rose, D. W., Hooshmand, F., Aggarwal, A. K., and Rosenfeld, M. G. (2000) Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification, Science 290, 1127-1131.
[85] Khazanov, N., and Levy, Y. (2011) Sliding of p53 along DNA can be modulated by its oligomeric state and by cross-talks between its constituent domains, J. Mol. Biol. 408, 335-355.
[86] Terakawa, T., Kenzaki, H., and Takada, S. (2012) p53 searches on DNA by rotation-uncoupled sliding at C-terminal tails and restricted hopping of core domains, J Am Chem Soc 134, 14555-14562.
[87] Mangel, W. F., McGrath, W. J., Xiong, K., Graziano, V., and Blainey, P. C. (2016) Molecular sled is an eleven-amino acid vehicle facilitating biochemical interactions via sliding components along DNA, Nat Commun 7, 10202.
[88] Dang, C. V., and Lee, W. M. (1989) Nuclear and nucleolar targeting sequences of erb-A, c-myb, N-myc, p53, HSP70, and HIV tat proteins, J. Biol. Chem. 264, 18019-18023.
[89] Marine, J. C. (2010) p53 stabilization: the importance of nuclear import, Cell Death Differ 17, 191-192.
[90] Regeling, A., Armata, H. L., Gallant, J., Jones, S. N., and Sluss, H. K. (2011) Mice defective in p53 nuclear localization signal 1 exhibit exencephaly, Transgenic Res 20, 899-912.
[91] Wang, P., Reed, M., Wang, Y., Mayr, G., Stenger, J. E., Anderson, M. E., Schwedes, J. F., and Tegtmeyer, P. (1994) p53 domains: structure, oligomerization, and transformation, Mol. Cell.
Biol. 14, 5182-5191.
[92] Bell, S., Hansen, S., and Buchner, J. (2002) Refolding and structural characterization of the human p53 tumor suppressor protein, Biophys. Chem. 96, 243-257.
[93] Cho, Y. J., Gorina, S., Jeffrey, P. D., and Pavletich, N. P. (1994) CRYSTAL-STRUCTURE OF A P53 TUMOR-SUPPRESSOR DNA COMPLEX - UNDERSTANDING TUMORIGENIC MUTATIONS, Science 265, 346-355.
[94] Chen, Y., Dey, R., and Chen, L. (2010) Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer, Structure 18, 246-256.
[95] Chen, Y. H., Zhang, X. J., Machado, A. C. D., Ding, Y., Chen, Z. C., Qin, P. Z., Rohs, R., and Chen, L. (2013) Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion, Nucleic Acids Res. 41, 8368-8376.
[96] Vainer, R., Cohen, S., Shahar, A., Zarivach, R., and Arbely, E. (2016) Structural Basis for p53 Lys120-Acetylation-Dependent DNA-Binding Mode, J. Mol. Biol. 428, 3013-3025.
[97] Aramayo, R., Sherman, M. B., Brownless, K., Lurz, R., Okorokov, A. L., and Orlova, E. V.
(2011) Quaternary structure of the specific p53-DNA complex reveals the mechanism of p53 mutant dominance, Nucleic Acids Res 39, 8960-8971.
[98] Martin, T. G., Bharat, T. A., Joerger, A. C., Bai, X. C., Praetorius, F., Fersht, A. R., Dietz, H., and Scheres, S. H. (2016) Design of a molecular support for cryo-EM structure determination, Proc. Natl. Acad. Sci. U. S. A. 113, E7456-e7463.
[99] Kim, H., Kim, K., Choi, J., Heo, K., Baek, H. J., Roeder, R. G., and An, W. (2012) p53 requires an intact C-terminal domain for DNA binding and transactivation, J. Mol. Biol. 415, 843-854.
[100] Vuzman, D., and Levy, Y. (2012) Intrinsically disordered regions as affinity tuners in protein-DNA interactions, Mol Biosyst 8, 47-57.
[101] Liu, Q., Segal, D. J., Ghiara, J. B., and Barbas, C. F., 3rd. (1997) Design of polydactyl zinc-finger proteins for unique addressing within complex genomes, Proc. Natl. Acad. Sci. U. S.
A. 94, 5525-5530.
[102] Kim, J. S., and Pabo, C. O. (1998) Getting a handhold on DNA: design of poly-zinc finger proteins with femtomolar dissociation constants, Proc. Natl. Acad. Sci. U. S. A. 95, 2812-2817.
[103] Wolfe, S. A., Ramm, E. I., and Pabo, C. O. (2000) Combining structure-based design with phage display to create new Cys(2)His(2) zinc finger dimers, Structure 8, 739-750.
[104] Imanishi, M., Hori, Y., Nagaoka, M., and Sugiura, Y. (2000) DNA-bending finger: artificial design of 6-zinc finger peptides with polyglycine linker and induction of DNA bending, Biochemistry 39, 4383-4390.
[105] Nagaoka, M., Kaji, T., Imanishi, M., Hori, Y., Nomura, W., and Sugiura, Y. (2001) Multiconnection of identical zinc finger: implication for DNA binding affinity and unit modulation of the three zinc finger domain, Biochemistry 40, 2932-2941.
[106] Moore, M., Choo, Y., and Klug, A. (2001) Design of polyzinc finger peptides with structured linkers, Proc. Natl. Acad. Sci. U. S. A. 98, 1432-1436.
[107] Imanishi, M., Yan, W., Morisaki, T., and Sugiura, Y. (2005) An artificial six-zinc finger peptide with polyarginine linker: selective binding to the discontinuous DNA sequences, Biochem.
Biophys. Res. Commun. 333, 167-173.
[108] Nakatsukasa, T., Shiraishi, Y., Negi, S., Imanishi, M., Futaki, S., and Sugiura, Y. (2005) Site-specific DNA cleavage by artificial zinc finger-type nuclease with cerium-binding peptide, Biochem. Biophys. Res. Commun. 330, 247-252.
[109] Shimizu, Y., Bhakta, M. S., and Segal, D. J. (2009) Restricted spacer tolerance of a zinc finger nuclease with a six amino acid linker, Bioorg. Med. Chem. Lett. 19, 3970-3972.
[110] Nomura, W., Masuda, A., Ohba, K., Urabe, A., Ito, N., Ryo, A., Yamamoto, N., and Tamamura, H. (2012) Effects of DNA binding of the zinc finger and linkers for domain fusion on the catalytic activity of sequence-specific chimeric recombinases determined by a facile fluorescent system, Biochemistry 51, 1510-1517.
[111] Pomerantz, J. L., Sharp, P. A., and Pabo, C. O. (1995) Structure-based design of transcription factors, Science 267, 93-96.
[112] Robinson, C. R., and Sauer, R. T. (1996) Covalent attachment of Arc repressor subunits by a peptide linker enhances affinity for operator DNA, Biochemistry 35, 109-116.
[113] Vuzman, D., and Levy, Y. (2010) DNA search efficiency is modulated by charge composition and distribution in the intrinsically disordered tail, Proc Natl Acad Sci U S A 107, 21004-21009.
[114] Halford, S. E., and Marko, J. F. (2004) How do site-specific DNA-binding proteins find their targets?, Nucleic Acids Res. 32, 3040-3052.
[115] Hammar, P., Leroy, P., Mahmutovic, A., Marklund, E. G., Berg, O. G., and Elf, J. (2012) The Lac repressor displays facilitated diffusion in living cells, Science 336, 1595-1598.
[116] Normanno, D., Boudarene, L., Dugast-Darzacq, C., Chen, J., Richter, C., Proux, F., Benichou, O., Voituriez, R., Darzacq, X., and Dahan, M. (2015) Probing the target search of DNA-binding proteins in mammalian cells using TetR as model searcher, Nat Commun 6, 7357.
[117] Wang, Y. M., Austin, R. H., and Cox, E. C. (2006) Single molecule measurements of repressor protein 1D diffusion on DNA, Phys. Rev. Lett. 97, 048302.
[118] Greene, E. C., Wind, S., Fazio, T., Gorman, J., and Visnapuu, M. L. (2010) DNA curtains for high-throughput single-molecule optical imaging, Methods Enzymol. 472, 293-315.
[119] Forget, A. L., and Kowalczykowski, S. C. (2012) Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search, Nature 482, 423-427.
[120] Lee, A. J., and Wallace, S. S. (2016) Visualizing the Search for Radiation-damaged DNA Bases in Real Time, Radiat. Phys. Chem. Oxf. Engl. 1993 128, 126-133.
[121] Cuculis, L., Abil, Z., Zhao, H., and Schroeder, C. M. (2016) TALE proteins search DNA using a rotationally decoupled mechanism, Nat. Chem. Biol. 12, 831-837.
[122] Ahmadi, A., Rosnes, I., Blicher, P., Diekmann, R., Schüttpelz, M., Glette, K., Tørresen, J., Bjørås, M., Dalhus, B., and Rowe, A. D. (2018) Breaking the speed limit with multimode fast scanning of DNA by Endonuclease V, Nat. Commun. 9.
[123] Kamagata, K., Mano, E., Ouchi, K., Kanbayashi, S., and Johnson, R. C. (2018) High Free-Energy Barrier of 1D Diffusion Along DNA by Architectural DNA-Binding Proteins, J. Mol.
Biol. 430, 655-667.
[124] Takada, S., Kanada, R., Tan, C., Terakawa, T., Li, W., and Kenzaki, H. (2015) Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations, Acc. Chem. Res. 48, 3026-3035.
[125] Schreiber, G. (2002) Kinetic studies of protein-protein interactions, Current Opinion in Structural Biology 12, 41--47.
[126] Ubbink, M. (2009) The courtship of proteins: Understanding the encounter complex, FEBS Letters 583, 1060--1066.
[127] Kiel, C., Selzer T., Shaul Y., Schreiber G., and Herrmann C. (2004) Electrostatically optimized Ras-binding Ral guanine dissociation stimulator mutants increase the rate of association by stabilizing the encounter complex, Proceedings of the National Academy of Sciences of the United States of America 101, 9223--9228.
[128] Clore, G. M., Tang, C., and Iwahara, J. (2007) Elucidating transient macromolecular interactions using paramagnetic relaxation enhancement, Current Opinion in Structural Biology 17, 603--616.
[129] Chun Tang, J. I. G. M. C. (2006) Visualization of transient encounter complexes in protein–
protein association, Nature 444, 383-386.
[130] Volkov, A. N., Worrall, J. A. R., Holtzmann, E., and Ubbink, M. (2006) Solution structure and dynamics of the complex between cytochrome c and cytochrome c peroxidase determined by paramagnetic NMR, Proceedings of the National Academy of Sciences of the United States of
[131] Hulsker, R., Baranova, M. V., Bullerjahn , G. S., and Ubbink, M. (2008) Dynamics in the transient complex of plastocyanin-cytochrome f from Prochlorothrix hollandica, Journal of the American Chemical Society 130, 1985--1991.
[132] Kim, Y. C., Tang, C., Clore, G. M., and Hummer, G. (2008) Replica exchange simulations of transient encounter complexes in protein-protein association, Proceedings of the National Academy of Sciences of the United States of America 105, 12855--12860.
[133] Tempestini, A., Monico, C., Gardini, L., Vanzi, F., Pavone, F. S., and Capitanio, M. (2018) Sliding of a single lac repressor protein along DNA is tuned by DNA sequence and molecular switching, Nucleic Acids Res. 46, 5001-5011.
[134] Bonnet, I., Biebricher, A., Porte, P.-L., Loverdo, C., Benichou, O., Voituriez, R., Escude, C., Wende, W., Pingoud, A., and Desbiolles, P. (2008) Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA, Nucleic Acids Res. 36, 4118-4127.
[135] Rajagopalan, S., Huang, F., and Fersht, A. R. (2011) Single-Molecule characterization of oligomerization kinetics and equilibria of the tumor suppressor p53, Nucleic Acids Res. 39, 2294-2303.
[136] Kamagata, K., Kanbayashi, S., Honda, M., Itoh, Y., and Takahashi, H. (2020) Liquid-like droplet formation by tumor suppressor p53 induced by multivalent electrostatic interactions between two disordered domains, Scientific Reports, 1--12.
[137] Blainey, P. C., Van Oijen, A. M., Banerjee, A., Verdine, G. L., and Xie, X. S. (2006) A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA, Proceedings of the National Academy of Sciences of the United States of America 103, 5752--5757.
[138] Blainey, P. C., van Oijent, A. M., Banerjee, A., Verdine, G. L., and Xie, X. S. (2006) A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA, Proc. Natl. Acad. Sci. U. S. A. 103, 5752-5757.
[139] Blainey, P. C., Luo, G., Kou, S. C., Mangel, W. F., Verdine, G. L., Bagchi, B., and Xie, X. S.
(2009) Nonspecifically bound proteins spin while diffusing along DNA, Nat. Struct. Mol.
Biol. 16, 1224-1229.
[140] Thompson, R. E., Larson, D. R., and Webb, W. W. (2002) Precise nanometer localization analysis for individual fluorescent probes, Biophys. J. 82, 2775-2783.
[141] Ahmadi, A., Rosnes, I., Blicher, P., Diekmann, R., Schüttpelz, M., Glette, K., Tørresen, J., Bjørås, M., Dalhus, B., and Rowe, A. D. (2018) Breaking the speed limit with multimode fast scanning of DNA by Endonuclease V, Nat Commun 9.
[142] Schreiber, G. (2002) Kinetic studies of protein-protein interactions, Curr. Opin. Struct. Biol.
12, 41-47.
[143] Sugase, K., Dyson, H. J., and Wright, P. E. (2007) Mechanism of coupled folding and binding of an intrinsically disordered protein, Nature 447, 1021-1025.
[144] Spoerner, M., Herrmann, C., Vetter, I. R., Kalbitzer, H. R., and Wittinghofer, A. (2001) Dynamic properties of the Ras switch I region and its importance for binding to effectors, Proc. Natl. Acad. Sci. U. S. A. 98, 4944-4949.
[145] Ali Azam, T., Iwata, A., Nishimura, A., Ueda, S., and Ishihama, A. (1999) Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid, J. Bacteriol. 181, 6361-6370.
[146] Shivaswamy, S., Bhinge, A., Zhao, Y., Jones, S., Hirst, M., and Iyer, V. R. (2008) Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation, PLoS Biol. 6, e65.
[147] Nili, E. L., Oren, M., Field, Y., Lubling, Y., Widom, J., and Segal, E. (2010) p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy, Genome Research 20, 1361--1368.
[148] Laptenko, O., Beckerman, R., Freulich, E., and Prives, C. (2011) P53 Binding To Nucleosomes Within the P21 Promoter in Vivo Leads To Nucleosome Loss and Transcriptional Activation, Proceedings of the National Academy of Sciences of the United States of America 108, 10385--10390.
[149] Mazza, D., Alice, A., Nicole, G., Tatsuya, M., and G., M. J. (2012) A benchmark for chromatin binding measurements in live cells, Nucleic Acid Research 40, 1-13.
[150] Kanada, R., Terakawa, T., Kenzaki, H., and Takada, S. (2019) Nucleosome crowding in chromatin slows the diffusion but can promote target search of proteins, Biophysical Journal, 1--11.
Publication list
1. Nabanita Sadhukhan, Takahiro Muraoka, Daisuke Abe, Yuji Sasanuma, Dwiky Rendra Graha Subekti, and Kazushi Kinbara, “Thermoresponsive Self-assembly and
Conformational Changes of Amphiphilic Monodisperse Short Poly(ethlene glycol)s in Water”, Chemistry Letters, CSJ Journals, vol. 43 No.7, 1055-1057, (2014).
2. Chihiro Igarashi, Agato Murata, Yuji Itoh, Dwiky Rendra Graha Subekti, Satoshi
Takahashi, and Kiyoto Kamagata, “DNA garden: A simple method for producing arrays of stretchable DNA for single-molecule fluorescence imaging of DNA binding proteins”, Bull.
Chem. Soc. Jpn., CSJ Journals, vol. 90, 34-43, (2017).
3. Dwiky Rendra Graha Subekti, Agato Murata, Yuji Itoh, Satoshi Fukuchi, Hiroto
Takahashi, Saori Kanbayashi, Satoshi Takahashi, Kiyoto Kamagata, “Disordered linker in p53 participates in non-specific binding to and 1D sliding along DNA revealed by single-molecule fluorescence measurements”, Biochemistry, ACS Journals, vol. 56 (32), 4134-4144, (2017).
4. 鎌形清人、伊藤優志、Dwiky Rendra Graha Subekti、「がん抑制タンパク質 p53 はどの ように標的 DNA 配列探索問題を解いているのか? 」、日本物理学会誌 、 74(7)、 472 – 475, (2019).
5. Kiyoto Kamagata, Yuji Itoh, and Subekti Dwiky Rendra Graha, "How p53 Molecules Solve the Target DNA Search Problem: A Review", Int. J. Mol. Sci, 21(3), 1031, (2020).
6. Dwiky Rendra Graha Subekti, Agato Murata, Yuji Itoh, Satoshi Takahashi, and Kiyoto Kamagata, “Transient binding and jumping dynamics of p53 along DNA revealed by sub-millisecond resolved single-molecule fluorescence tracking”, Sci. Rep., Accepted (2020)