Search

Your search keyword '"Taylor, R. H."' showing total 620 results
Start Over Author "Taylor, R. H."
620 results on '"Taylor, R. H."'

13. Combating COVID-19-The role of robotics in managing public health and infectious diseases

Author

Yang, G. -Z, Nelson, B. J., Murphy, R. R., Choset, H., Christensen, H., Collins, S. H., Dario, P., Goldberg, K., Ikuta, K., Jacobstein, N., Kragic, Danica, Taylor, R. H., McNutt, M., Yang, G. -Z, Nelson, B. J., Murphy, R. R., Choset, H., Christensen, H., Collins, S. H., Dario, P., Goldberg, K., Ikuta, K., Jacobstein, N., Kragic, Danica, Taylor, R. H., and McNutt, M.

Abstract

COVID-19 may drive sustained research in robotics to address risks of infectious diseases., QC 20200626

Published
2020
Full Text
View/download PDF

15. High-Temperature Properties and Applications of Polymeric Materials

Author

MARTIN R. TANT, JOHN W. CONNELL, HUGH L. N. MCMANUS, Martin R. Tant, Hugh L. N. McManus, Martin E. Rogers, R. E. Taylor, R. H. Bogaard, Shaow B. Lin, Robert Czarnek, A. J. Hill, M. R. Kamal, W. Frydrychowicz, I. Ansari, Hugh L. N. McManus, David S. Tai, J. R. Lee, R. G. Kander, J. M. Kenny, L. Torre and MARTIN R. TANT, JOHN W. CONNELL, HUGH L. N. MCMANUS, Martin R. Tant, Hugh L. N. McManus, Martin E. Rogers, R. E. Taylor, R. H. Bogaard, Shaow B. Lin, Robert Czarnek, A. J. Hill, M. R. Kamal, W. Frydrychowicz, I. Ansari, Hugh L. N. McManus, David S. Tai, J. R. Lee, R. G. Kander, J. M. Kenny, L. Torre

Published
1995

20. The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity

Author

Gary G. Chiang, Masoud Vedadi, Alberto Martin, Dalia Barsyte-Lovejoy, William N. Pappano, Cheryl H. Arrowsmith, Alexander Nuber, Vijayaratnam Santhakumar, Kenneth M. Comess, Judd C. Rice, Maricel Torrent, Gunnar Schotta, Peter Brown, Conglei Li, Anup K. Upadhyay, Fengling Li, Alex R Shoemaker, Ramzi F. Sweis, Mikkel Algire, Yujia Dai, Loren M. Lasko, Taylor R H Mitchell, Creighton T. Tuzon, Kenneth D. Bromberg, Mohammad S. Eram, Michael R. Michaelides, Niru B. Soni, Clarissa G. Jakob, Chaohong Sun, Manisha A Jhala, and Vlasios Manaves

Subjects
Models, Molecular, 0301 basic medicine, Methyltransferase, DNA Repair, DNA repair, Crystallography, X-Ray, Heterocyclic Compounds, 4 or More Rings, Methylation, Genomic Instability, Epigenesis, Genetic, 03 medical and health sciences, Transcription (biology), Cell Line, Tumor, Histone H2A, Humans, Epigenetics, Enzyme Inhibitors, Molecular Biology, Molecular Structure, biology, Histone-Lysine N-Methyltransferase, Cell Biology, Cell biology, 030104 developmental biology, Histone, Histone methyltransferase, biology.protein
Abstract

Protein lysine methyltransferases (PKMTs) regulate diverse physiological processes including transcription and the maintenance of genomic integrity. Genetic studies suggest that the PKMTs SUV420H1 and SUV420H2 facilitate proficient nonhomologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation (me2 and me3, respectively) of lysine 20 on histone 4 (H4K20). Here we report the identification of A-196, a potent and selective inhibitor of SUV420H1 and SUV420H2. Biochemical and co-crystallization analyses demonstrate that A-196 is a substrate-competitive inhibitor of both SUV4-20 enzymes. In cells, A-196 induced a global decrease in H4K20me2 and H4K20me3 and a concomitant increase in H4K20me1. A-196 inhibited 53BP1 foci formation upon ionizing radiation and reduced NHEJ-mediated DNA-break repair but did not affect homology-directed repair. These results demonstrate the role of SUV4-20 enzymatic activity in H4K20 methylation and DNA repair. A-196 represents a first-in-class chemical probe of SUV4-20 to investigate the role of histone methyltransferases in genomic integrity.

Published
2017

21. Electron spin resonance studies of some magnetic alloys

Author

Taylor, R. H.

Subjects
546
Abstract

A study has been made of the X-band esr behaviour of a number of dilute alloys and intermetallic compounds containing s-state ions between 300K and 1.7K. A large negative g-shift has been observed in the most dilute alloys of Gd in Pd (to 1.77); the g-shift reducing at higher concentrations of Gd as the Pd d-band is filled. A positive g-shift has been observed in the Pd-Mn (to 2.15) and LaAl₂-Gd systems. The sign of the g-shifts has been related to theory. The temperature dependence of the g-value and linewidth in Pd-Gd and Pd-Mn alloys has been interpreted in terms of the effect of the increase in demagnetising fields in the particles of the sample at the onset of ferromagnetic order. The esr measurements in Pd-Mn show a form consistent with an increasing magnetisation in a field of 3KGauss at concentrations above 3at% Eh, in contrast to the results of static susceptibility measurements. Comparison of the present results with previous data suggests that in these dilute alloys there may be a frequency dependent contribution to the residual linewidth. The g-value and temperature dependence of the linewidth has been measured for a number of compounds. Characteristic forms of behaviour have been distinguished for ferromaenets (including GdA1₂, GdPt₂, GdCu₆, EuPd₂, EuPd and Pd₂MnSn) and antiferromagnets (including GdAg₃, GdCu₂, GdB₆, GdB₄, GdZn₁₂, Gd₂Zn₁7 and "GdCu₄"). In the last five antiferromagnets an increase in linewidth at temperatures far above the Neel point has been observed and tentatively interpreted in terms of an extended regime of short-range order. For a number of the compoundsl ordering temperatures have been predicted from the esr results. The compound GdPd₃ showed anomalous behaviour possibly characteristic of metamagnetism. Compounds of Lh in Zn showed completely anomalous esr behaviour.

Published
1972

23. CSB cooperates with SMARCAL1 to maintain telomere stability in ALT cells

Author

Jian Qin, Nicole L. Batenburg, John R. Walker, Taylor R. H. Mitchell, Angus Ho, Xu-Dong Zhu, and Emily Feng

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, 0303 health sciences, DNA Repair, 030302 biochemistry & molecular biology, nutritional and metabolic diseases, Telomere Homeostasis, Cell Biology, Biology, Telomere, Endonucleases, MUS81, Chromatin, Cell biology, 03 medical and health sciences, Cancer cell, Endonuclease complex, Phosphorylation, ERCC6, Homologous recombination, Homologous Recombination, 030304 developmental biology
Abstract

Elevated replication stress is evident at telomeres of about 10-15% of cancer cells, which maintain their telomeres via a homologous recombination (HR)-based mechanism, referred to as alternative lengthening of telomeres (ALT). How ALT cells resolve replication stress to support their growth remains incompletely characterized. Here, we report that CSB (also known as ERCC6) promotes recruitment of HR repair proteins (MRN, BRCA1, BLM and RPA32) and POLD3 to ALT telomeres, a process that requires the ATPase activity of CSB and is controlled by ATM- and CDK2-dependent phosphorylation. Loss of CSB stimulates telomeric recruitment of MUS81 and SLX4, components of the structure-specific MUS81-EME1-SLX1-SLX4 (MUS-SLX) endonuclease complex, suggesting that CSB restricts MUS-SLX-mediated processing of stalled forks at ALT telomeres. Loss of CSB coupled with depletion of SMARCAL1, a chromatin remodeler implicated in catalyzing regression of stalled forks, synergistically promotes not only telomeric recruitment of MUS81 but also the formation of fragile telomeres, the latter of which is reported to arise from fork stalling. These results altogether suggest that CSB-mediated HR repair and SMARCAL1-mediated fork regression cooperate to prevent stalled forks from being processed into fragile telomeres in ALT cells.

Published
2019

26. Abstracts

Author

Korzeniewski, P., Lang, S. A., Grant, R., Loader, C., Vaghadia, H., Wong, D., Waters, T., Merrick, P., Ali, M. J., Dobkowski, W., Cornelius, T., Hawkins, R., Varkey, G. P., Claffey, Liam, Plourde, Gilles, Trahan, Michel, Morris, Joan, Dean, Deanne M., Yamaguchi, Hiroshi, Harukuni, Izumi, Naito, Hiroshi, Chan, V. W. S., Mati, N., Seyone, C., Evans, D., Chung, F., Joffe, D., Plourde, G., Villemurc, C., Hong, M., Milne, B., Loomis, C., Jhamandas, K., Priddy, R., Archer, D., Tang, T., Sabourin, M., Samanini, N., Cuillerier, D. J., Schuben, Armin, Awad, Issam A., Perez-Trepichio, Alejandro D., Ebrahim, Zeyd Y., Bloomfield, Eric L., Zexu, Fang, Zhengnua, Gu, Qing, Zou, Balhua, Sung, Miller, D. R., Martineau, R. J., Wynands, J. E., Hill, J. D., Knill, R. L., Skinner, M. I., Novick, T. V., McLean, R. F., Kolton, M., Noble, W. H., Sullivan, P. J., Cheng, D. C. H., Chapman, K. R., Ong, D., Roraanelli, J., Smallman, Bettina, Nathan, Howard J., Murphy, J. T., Hall, R. I., Moffitt, E. A., Hudson, R. J., Pascoe, E. A., Anderson, B. A., Thomson, I. R., Kassum, D. A., Shanks, A., Rosenbloom, M., Sidi, A., Gehrig, T. R., Fool, J. M., Rush, W., Martin, A. J., Cooper, P. D., Maltby, J. R., Johnson, D., Hurst, T., Mayers, I., Wigglesworth, D. F., Rose, D. K., Kay, J. C., Mazer, C. D., Yang, H., Beattie, W. S., Doyle, D. John, Demajo, Wlifred, Comfort, V. Kim, Code, William E., Rooney, Michael E., Clark, F. J. S., Sutton, I. R., Mutch, W. A. C., Thomson, I. R., Teskey, J. M., Thiessen, O. B., Rosanbloom, M., Tang, T. K. K., Robblee, J. A., Nathan, H. J., Wynands, J. E., Eagle, C. J., Belenkle, I., Chan, K. L., Tyberg, J. V., Stockwell, M., Zintel, T., Gallagher, G., Kavanagh, B., Sandier, A., Lawson, S., Chung, F., Ong, D., Isabel, L., Trépanier, C. A., Campbell, David C., Randall, Thomas E., Growe, Gershon H., Scarth, Irene, Sawchuk C. W. T., Ong B., Unruh H., Horan T., Greengrass R., Mark, D., Kitts, J. B., Curran, M. J., Lindsay, P., Polis, T., Coté, Sylvain, Socci, Maria, Wiesel, Saul, Conway, J. B., Seyone, C., Goldberg, J., Chung, F., Rose, D. Keith, Cohen, Marsha M., Rogers, Kent H., Duncan P. G., Pope W. D. B., Tweed W. A., Biehl D., Novick, T. V., Skinner, M. I., Mathieu, Alix, Villeneuve, Edith, Goldsmith, Charles H., Allen, Gregory C., Smith, Charles E., Pinchak, Alfred C., Hagen, Joan F., Hudson, J. C., Gennings, C., Tyler, B. L., Keenan, R. L., Chung, F., Seyone, C., Matl, N., Ong, D., Powell, P., Tessler, M. J., Kleiman, S. J., Wiesel, S., Tetzlaff, John E., Yoon, Helen J., Baird, Bruce, Walsh, Michael, Hondorp, Gregory, Wassef, Medhat R., Munshi, C., Brooks, J., Nimphius, N., Tweed, W. A., Lee, T. L., Tweed, W. A., Phua, W. T., Chong, K. Y., Lim, E., Finegan, B. A., Coulson, C., Lopaschuk, G. D., Clanachan, A. S., Fournier L., Cloutier R., Major D., Sharpe, M. D., Wexler, H. R., Dhamee, M. Saeed, Rooney, R., Ong, S. K., O’Leary, E., McCarroll, M., Phelan, D., Young, T., Coghlan, D., O’Leary, E., Blunnie, W. P., Splinter, W. M., Splinter, W. M., Ryan T., Maguire M., Bouchier-Hayes D., Cunningham A. J., Kamath, M. V., Fallen, E. L., Murkin, J. M., Shannon, N. A., Montgomery, C. J., Karl, H. W., Raymond, Jacques, Drolet, Pierre, Tanguay, M., Blaise, G., Garceau, D., Dumont, L., Omri, A., Sharkawi, M., Billard, V., Bourgain, J. L., Panos, A., Mazer, C. D., Lichtenstein, S. V., Bevan, J. C., Popovic, V., Baxter, M. R. N., Donati, F., Bevan, D. R., Bachman, C., Kopelow, M., Donen, N., Umôn, D. T., Kemp, S., Hartley, E., Sikich, N., Roy, W. L., Lerman, J., Cooper, Richard M., Yentis, S. M., Bissonnette, B., Halpern, L., Roy, L., Burrows, F. A., Fear, D. W., Hillier, S., Sloan, M., Crawford, M., Blssonnette, B., Sikich, N., Friedlander, M., Sandier, A. N., Panos, L., Winton, T., Benureof, J., Karski J., Teasdale S., Cruise C., Skala R., Zulys V., Ong, D., Chow, F., Packota, G., Yip, R., Bradley, J., Arellano, R., Sussman, G., Sosis, M., Braverman, B., Sosis, M., Ivankovich, A. D., Manganas, M., Lephay, A., Fournier, Th., Kadri, N., Ossart, M., Sandier, A. N., Turner, K. E., Wick, V., Wherrett, C., Sullivan, P. J., Dyck, J. B., Varvel, J., Shafer, S. L., Fiset, P., Balendran, P., Meistelman, C., Lira, E., Sloan, M., Nigrovic, V., Banoub, M., Splinter, W. M., Roberts, D. W., Rhine, E. J., MacNeill, H. B., Bonn, G. E., Clarke, W. M., Noel, L. P., Ryan T., Moriarty J., Bouchier-Hayes D., Cunningham A. J., Sandier, A. N., Baxter, A. D., Norman, P., Samson, B., Hull, K., Chung, F., Mali, N., Evans, D., Cruise, C., Shumka, D., Seyone, C., Leung, Peter T., Badner, N. H., Komar, W. E., Rajasingham, M., Farren, B., Vaillancourt, G., Cournoyer, S., Hollmann, C., Breen, T. W., Janzen, J. A., Crochetiere, C. T., McMorland, G. H., Douglas, M. J., Kamani, A. A., Arora, Sunil K., Tunstall, M., Ross, J., Mayer, D. C., Weeks, S. K., Norman, P., Daley, D., Sandier, A., Guay, J., Gaudreault, P., Boulanger, A., Tang, A., Lortie, L., Dupuis, C., Backman, S. B., Bachoo, M., Polosa, C., Moudgil, G. C., Frame, B., Blajchman, H. A., Singal, D. P., Albert, J. -F., Ratcliff, A., Law, J. -C., Varvel, J., Hung, O., Shafer, S. L., Fiset, P., Balendran, P., Burgess, P. M., Doak, G. J., Duke, P. C., Sloan, P. A., Mather, L. E., McLean, C. F., Rutten, A. J., Nation, R. L., Milne, R. W., Runciman, W. B., Somoggi, A. A., Haack, Carol, Shafer, Steven L., Irish, Craig L., Weisleider, Louis, Mazer, C. David, Bell, Robert S., Dejonckheere, M., Levarlet, M., d’Hollander, A., Taylor, R. H., Sikich, N., Campbell, F., McLeod, M. E., Swartz, J., Spahr-Schopfer, I., McIntyre, B. G., Roy, W. L., Laycock, G. J. A., Mitchell, I. M., Morton, N. S., Logan, R. W., Campbell, F., Yentis, S. M., Fear, D., Halpem, L., Sloan, M., Badgwell, J. Michael, Kleinman, Sam, Yentis, S. M., Britton, J. T., Hannallah, R. S., Schafer, P. O., Norden, J. M., Splinter, W. M., Menard, E. A., Derdamezi, J. B., Ghurch, J. G., Britt, B. A., Radde, I. C., Sosis, M., Kao, Y. James, Norton, Richard G., Volgyesi, G. A., Spahr-Schopfer, I., Sosis, M., Plum, Mark, Sosis, M., Smith, C. E., Pinchak, A. C., Hancock, D. E., Owen, P., McMeekin, J., Hanson, S., Cujec, B., Feindel, C. M., Cruz, J., Boylen, P., Ong, D., Murphy, J. T., Dupuis, J. Y., Nathan, H. J., Cattran, C., Wynands, J. E., Murphy, J. T., Kinley, C. E., Sulliyan, J. A., Landymore, R. W., Robblee, James A., Labow, Rosalind, Buckley, D. N., Sharpe, M. D., Guiraudon, G., Klein, G., Yee, R., Black, J., Devitt, J. H., McLellan, B. A., Dubbin, J., Ehrlich, L. E., Ralley, F. E., Robbins, G. R., Symcs, J. F., Bourke, M., Nathan, H., Wynands, J. E., Maritime Heart Centre, and Maritime Heart Centre

Published
1991
Full Text
View/download PDF

28. Abstracts

Author

Lacombe, P., Blaise, G., Plante, F., Hollmann, C., Penning, D. H., Patrick, J., Brien, J., Orser, B., Bertlik, M., Fedorko, L., O’Brodovich, H., Santos, A. C., Pedersen, H., Morishima, H. O., Finster, M., Arthur, G. R., Covino, B. G., Perreault, C., Albert, J. F., Couture, P., Meloche, R., Elliott, R. D., Stockwell, M., Roy, W. L., Lerman, J., McIntyre, B. G., Yee, D. A., Hunziker, P., Koch, J. P., Devitt, J. H., Daley, M. D., Colmenares, M. E., Norman, P. H., Sandler, A. N., Oyston, J. P., Knill, R. L., Skinner, M. I., Novick, T., Vandenberghe, H. M., Moote, C. A., Donati, François, Meistelman, Claude, Plaud, Benoit, Guay, J., Reinberg, C., Rivard, G. E., Poitras, B., Mathews, S., David, M., Dawe, G., Hall, R. I., Stringer D. G., Sandler A. N., Panos L., Lawson S., Einarson T. R., Badner N., Fiset, P., Balendran, P., Donati, F., Bevan, D. R., Hung, O. R., Varvel, J., Shafer, S., Stanski, D. R., Crawford, M. W., Carmichael, F. J., Orrego, H., Saldivia, V., Lerman, J., Ralley, F. E., Murkin, J. M., Hudson, R. J., Dunn, G., Perreault, L., Hardy, J. F., Donelly, M., Scott, W. A. C., Daly, D. S., McAllister, J. D., Sharpe, M. D., Manninen, P. H., Cuillerier, D. J., Gelb, A. W., Nantau, W. E., Leon, J. E., Bissonnette, B., Davies, K. R., Gelb, A., Boughner, D. R., Bisnaire, D., Shokeir, O., Code, W. E., Hertz, L., White, H. S., Hong, M., Milne, B., Loomis, C., Jhamandas, K., Lam A. M., Slee T., Hirst R., Cooper J. O., Pavlin E. G., Sundling N., Mutch, W. A. C., Ringaert, K., Ewart, F., White, I., Donen, N., Winn H. R., Grady M. S., Murkin, J. M., Farrar, J. K., McNeill, B., Lok, P., Nalder, B., Jivraj, K., Golar, S., Ford, G., Rosenal, T., Puchalski, S. A., Morison, D. H., Collins, R. M., Gascoyne, R. D., Taylor, R. H., Lerman, J., Gauthier R. A., Chung F., Dyck B., Romanelli J. R., Chapman K. R., Lavoie, J., Marcin, R., Tétrault, J. P., Murphy, I. L., Splinter, W. M., Segstro, R., Morley-Forster, P. K., Lu, G., Lessard, M. R., Trépanier, C. A., Brochu, J. G., Coté, J. J., Denault, P. H., Baribault, J. P., Gordon, A. R., O’Connor, J. P., Ramsay, J. G., Malcolm, I., Chang, P. C., Reynolds, F. B., Lang, S. A., Ha, H. C., Grant, R. P., Dolman, J. F., Harper, J. A., White, S. A., Parsons, D. G., Evans, K. G., Merrick, P., Trivedi, Narendra S., Halpern, Meyer, Robalino, Joffre, Shevde, Ketan, Wang, B. C., Hiller, J. M., Simon, E. J., Hillman, D. E., Li, D., Rosenberg, C., Turndorf, H., Penning, J. P., Nagasaka, Hiroshi, Yaksh, T. L., Forrest, J. B., Lam, L., Woo, J., Rifkind, A., Broadman, L., Hannallah, R., DeLeon, E., Reff, R., Tanaka, K., Watanabe, R., Harada, T., Dan, K., Aull, L., Woodward, E. R., Rout, R. W., Paulus, D. A., Reimer, E. J., Badner, N. H., Komar, W. E., Fancourt-Smith, P. F., McEwen, J. A., Warriner, C. B., Moore, R., Rosenblatt, M., Merai, B., Robalino, J., Shevde, K., Bryk, D., McCormack, J. P., Levine, M., Forster-Coull, J., Stasiuk, R. B. P., Jenkins, L. C., Chen, Kunzhou, Pan, Jianhui, Ji, Xuan, Vaidya, D., Tetzlaff, J. E., Baird, B. A., Yoon, H. J., Wood, G., Simpson, T., Pillow, K. J., Lampe, K. M., Hansen, L. M., Foldvari, M., Courtice, I. D., MacLeod, B. A., Panos L., Lawson S., Koren G., Volgyesi, G. A., Kolesar, R., Wolf, G. L., Sidebotham, G. W., Sprung, J., Gamulin, S., Bosnjak, Z. J., Kampine, J. P., Doyle, D. John, Harioka, T., Sone, T., Kakuyama, M., Miyake, C., Toda, H., Sosis, M., Oka, T., Ohwada, T., Kochi, A., Mizuguchi, T., Kay, J. C., Beauchamp, R. J., Mazer, C. D., Inada, E., Iwahashi, K., Aoki, K., Takanashi, S., Kohama, M., Aoki, Y., Poole, L., Murphy, J. T., Moffitt, E. A., Jolly, D., Finegan, B. A., Beach, J., Gulamhusein, S., Vincent, D., Sullivan, P. J., Martineau, R. J., Miller, D. R., Lewis, P., Staniland, J., Cuppage, A., Davies, J. M., Rose, D. K., Cohen, M. M., Rogers, K. H., Gellner, D., Duncan, P. G., Johnson, J. A., Cohen, J. A., Boisvenu, G., Haley, L. D., Parlow, J. L., Cervenko, F. W., Dillon, F., Harwood, T., Kolesar, R., Volgyesi, G., Reid, C. W., Samson, B., Beattie, W. S., Goldsmith, C. H., Sims, C. H., Welborn, L. G., Hannallah, R. S., Higgins, T., Fink, R., Luban, N., Murray, D. J., Forbes, R. B., Mehta, M., Dull, D. L., Horimoto, Y., Naide, M., Schaefer, J. D., Bonn, G. E., Rhine, E. J., MacNeill, H. B., Ménard, E. A., Roberts, D. J., Komocar, L., Kay, J., Chevrier, R., Marsh, B. J., Morton, N. S., White, M., Kenny, G. N. C., Yamashita, M., Tsuji, M., Malviya, S., Swartz, J., Brown, K. A., Holtby, H., Ein, S., Shandling, B., Smith, M. F., Beauprie, I. G., Clark, A. G., Keith, I. C., Spence, D., Ogata, Hiromaru, Midorikawa, Yukio, Doyle, D. John, Teves, Leonides Y., Jhawar, Balraj S., Kawamura, Takae, Wakusawa, Reiji, Hackmann, T., Steward, D. J., Maltby, J. R., Loken, R. G., Watson, N. C., Kubota, Tatsuya, Katano, Toshio, Yoshizawa, Mutsumi, Ohtake, Kazuei, Onodera, Fumio, Yoshitake, S., Matsumoto, S., Miyakawa, H., Takahashi, T., Kitano, T., Iwasaka, H., Hayano, Y., Noguchi, T., Taniguchi, K., Honda, N., Koyama, K., Takahashi, J., Ochiai, R., Takeda, J., Nagano, M., Rolbin, S., Hew, E., Morningstar, B., Mahesh, K., Yukioka, H., Fujimori, M., Siriwardhana, S. A., Kawas, A., Yates, S., Gulden, H., Upton, J. M., Giesecke, A. H., Suzuki, H., Maru, E., Fujita, M., Pagliarello, G., Simons, J., Irita, K., Shafiq, J., Tareen, F. M., Yoshitake, J., Suderman, V. S., Crosby, E. T., Mallon, J. S., Dunn, G. L., Hatano, Y., Nakamura, K., Nishiwada, M., Mori, Kenjiro, Pounder, D. R., Blackstock, D., Steward, D., Kumagai, M., Takinami, M., Tanaka, S., Shudo, Y., Amaki, Y., Kobayashi, K., Jansen, G. F. A., Kedaria, M., Zuurmond, W. W. A., Hartley, E., St. Louis, P., Rybczynski, J., McLeod, M. E., Byrick, R. J., Mullen, J. Brendan, Wong, P. Y., Wigglesworth, D., Kay, J. Colin, Swartz, J. S., Gold, M., Braude, B. M., Dolovich, J., Gilmour, R. F., Sutherland, L. R., O’Connor, G., Riding, K., Laird, B., Riou, S., Gross, Michael, Tang, T., Halpern, S. H., Roy, A. G., Côté, J. J., Lindblad, T., Buckley, D. N., Oxom, D. C., Whatley, G. S., Knox, J. W. D., Hooper, J. G. V., Dolman, J., Faneourt-Smith, P. F., Torsher, L., Gao, Yuhui, Chai, Xiaoqing, O’Leary, G., Qureshi, S. A., Laganiere, S., McGilveray, I., Boylan, J. F., Hassard, P., Teasdale, S. J., Kapnoudhis, P., Vaghadia, H., Turnbull, K. M., Villeneuve, E., Buluran, J., Amyot, Y., Tanguay, M., Pharm, B., Beique, G., Sidi, A., Rush, W., Clanachan, A. S., Duke, P. C., Leroux, M., Corne, R., Patton, N., Greenberg, D., Parrott, J., Desjardins, P., Merchant R. N., Brown W. F., Watson B. V., Burrows, F. A., Tatman, D. J., Starr, J. M., Symreng, T., Kall, R. I., Schweiger, I. M., Finlayson, D. C., Weisel, R. D., Ivanov, J., Mickle, D. A., Fuller, John, Lu, Grant, Dain, Steven, McLean, R. F., Noble, W. H., Kolton, M., Newfield, A. M., Lipton, J. M., Ide, T., Isono, S., Kochi, T., Izumi, Y., Erian, R. F., Stafford-Smith, M., Yamada, M., Johnson, D., Hurst, T., Mayers, I., Tsuda, Takako, Takeuchi, Mikio, Ishikawa, Kiyoshi, Ando, Hiroshi, Hanamura, Yasunori, Takasu, Hiroe, Hiyama, A., and Cardiac Anaesthesia Research Group

Published
1990
Full Text
View/download PDF

33. Methylated TRF2 associates with the nuclear matrix and serves as a potential biomarker for cellular senescence

Author

Taylor R. H. Mitchell and Xu-Dong Zhu

Subjects
Senescence, Aging, DNA damage, Fluorescent Antibody Technique, TRF2, Biology, Transfection, Methylation, Cell Line, 03 medical and health sciences, 0302 clinical medicine, cellular senescence, Humans, Telomeric Repeat Binding Protein 2, Cellular localization, 030304 developmental biology, 0303 health sciences, Cell Biology, Telomere, Shelterin, Nuclear matrix, Molecular biology, arginine methylation, 030220 oncology & carcinogenesis, nuclear matrix, Research Perspective, Cell aging, Biomarkers
Abstract

Methylation of N-terminal arginines of the shelterin component TRF2 is important for cellular proliferation. While TRF2 is found at telomeres, where it plays an essential role in maintaining telomere integrity, little is known about the cellular localization of methylated TRF2. Here we report that the majority of methylated TRF2 is resistant to extraction by high salt buffer and DNase I treatment, indicating that methylated TRF2 is tightly associated with the nuclear matrix. We show that methylated TRF2 drastically alters its nuclear staining as normal human primary fibroblast cells approach and enter replicative senescence. This altered nuclear staining, which is found to be overwhelmingly associated with misshapen nuclei and abnormal nuclear matrix folds, can be suppressed by hTERT and it is barely detectable in transformed and cancer cell lines. We find that dysfunctional telomeres and DNA damage, both of which are potent inducers of cellular senescence, promote the altered nuclear staining of methylated TRF2, which is dependent upon the ATM-mediated DNA damage response. Collectively, these results suggest that the altered nuclear staining of methylated TRF2 may represent ATM-mediated nuclear structural alteration associated with cellular senescence. Our data further imply that methylated TRF2 can serve as a potential biomarker for cellular senescence.

Published
2014

34. TRF1 phosphorylation on T271 modulates telomerase-dependent telomere length maintenance as well as the formation of ALT-associated PML bodies

Author

Xu-Dong Zhu, Florence R. Wilson, Stephanie L. Peragine, Taylor R. H. Mitchell, Kajaparan Jeyanthan, and Angus Ho

Subjects
0301 basic medicine, Telomerase, Intranuclear Inclusion Bodies, Plasma protein binding, Promyelocytic Leukemia Protein, medicine.disease_cause, Article, 03 medical and health sciences, Telomere Homeostasis, Cell Line, Tumor, medicine, Homeostasis, Humans, Telomeric Repeat Binding Protein 1, Threonine, Phosphorylation, Mutation, Multidisciplinary, Chemistry, Telomere, Cell biology, 030104 developmental biology, Cell culture, Tyrosine, HeLa Cells, Protein Binding
Abstract

TRF1, a component of the shelterin complex, plays a key role in both telomerase-dependent telomere maintenance and alternative lengthening of telomeres, the latter also known as ALT. Characteristics of ALT cells include C-circles and ALT-associated PML bodies, referred to as APBs. The function of TRF1 is tightly regulated by post-translational modification including phosphorylation, however TRF1 phosphorylation sites have yet to be fully characterized. Here we report a novel TRF1 phosphorylation site threonine 271. We show that a nonphosphorylatable mutation of T271A impairs TRF1 binding to telomeric DNA in vivo and renders TRF1 defective in inhibiting telomerase-dependent telomere elongation. On the other hand, TRF1 carrying a phosphomimic mutation of T271D is competent in not only binding to telomeric DNA but also inhibiting telomerase-mediated telomere lengthening. These results suggest that TRF1 phosphorylation on T271 negatively regulates telomerase-mediated telomere maintenance. We find that in telomerase-negative ALT cells, TRF1 carrying either a T271A or T271D mutation is able to promote C-circle production but fails to support APB formation. These results suggest that TRF1 phosphorylation on T271 is necessary for APB formation but dispensable for C-circle production. These results further imply that APB formation can be mechanistically separated from C-circle production.

Published
2016
Full Text
View/download PDF

37. Phosphorylated (pT371)TRF1 is recruited to sites of DNA damage to facilitate homologous recombination and checkpoint activation

Author

Megan McKerlie, John R. Walker, Xu-Dong Zhu, Florence R. Wilson, and Taylor R. H. Mitchell

Subjects
Cell cycle checkpoint, DNA repair, DNA damage, Poly ADP ribose polymerase, Ataxia Telangiectasia Mutated Proteins, Genome Integrity, Repair and Replication, Biology, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Genetics, Humans, DNA Breaks, Double-Stranded, Telomeric Repeat Binding Protein 1, Phosphorylation, 030304 developmental biology, 0303 health sciences, BRCA1 Protein, Intracellular Signaling Peptides and Proteins, Recombinational DNA Repair, Molecular biology, Chromatin, G2 Phase Cell Cycle Checkpoints, chemistry, 030220 oncology & carcinogenesis, Rad50, Tumor Suppressor p53-Binding Protein 1, Homologous recombination, DNA, HeLa Cells
Abstract

TRF1, a duplex telomeric DNA-binding protein, plays an important role in telomere metabolism. We have previously reported that a fraction of endogenous TRF1 can stably exist free of telomere chromatin when it is phosphorylated at T371 by Cdk1; however, the role of this telomere-free (pT371)TRF1 has yet to be fully characterized. Here we show that phosphorylated (pT371)TRF1 is recruited to sites of DNA damage, forming damage-induced foci in response to ionizing radiation (IR), etoposide and camptothecin. We find that IR-induced (pT371)TRF1 foci formation is dependent on the ATM- and Mre11/Rad50/Nbs1-mediated DNA damage response. While loss of functional BRCA1 impairs the formation of IR-induced (pT371)TRF1 foci, depletion of either 53BP1 or Rif1 stimulates IR-induced (pT371)TRF1 foci formation. In addition, we show that TRF1 depletion or the lack of its phosphorylation at T371 impairs DNA end resection and repair of nontelomeric DNA double-strand breaks by homologous recombination. The lack of TRF1 phosphorylation at T371 also hampers the activation of the G2/M checkpoint and sensitizes cells to PARP inhibition, IR and camptothecin. Collectively, these results reveal a novel but important function of phosphorylated (pT371)TRF1 in facilitating DNA double-strand break repair and the maintenance of genome integrity.

Published
2013

Catalog

Books, media, physical & digital resources
See catalog results