Ph.D., University of Southern California, 1991
University of California, Irvine
Irvine, CA 92697
Office: (949) 824-8215
UCI Faculty Profile: Kyoko Yokomori
The role of SMC family proteins in chromosome dynamics.
Chromosomes are essential components of the cell, storing genetic information necessary to carry out the normal life cycle of the cell. They serve as templates for replication and transcription, and undergo mitosis to maintain genetic information over generations. To achieve these multiple roles, chromosomes exhibit dynamic structural changes in a cell cycle-dependent manner. Although genetic studies identified various important cell cycle regulators such as cyclin and cdks, the actual molecular machine that drives structural changes of chromosomes in response to these cell cycle regulators remains elusive. In recent years, the SMC (structural maintenance of chromosomes) family proteins were found to play important roles in several fundamental chromosome functions including chromosome condensation, segregation, recombination, repair and X chromosome dosage compensation. The SMC proteins are physically associated with chromosomes, suggesting that they may be part of the machinery that regulates local and global structural changes of chromosomes required for these functions. The research objective of our laboratory is to biochemically identify and characterize the SMC-containing multiprotein complexes in human cells that modulate higher order chromatin structure, and study how their function is regulated during cell cycle using biochemical, cell biological and genetic approaches.
Our second goal is to establish an in vitro system to study the effect of higher order chromatin structure on gene expression. In conjunction with the study of the SMC family proteins, we will attempt to recaptiulate higher order chromatin structure and analyze its effect of transcription in vitro, utilizing an in vitro chromatin assembly and transcription system.
Schmiesing, J. A., Ball, A. R, Gregson, H. C., Alderton, J., Zhou, S., and Yokomori, K. (1998).
Identification of two distinct human SMC complexes involved in mitotic chromosome dynamics.
Proc. Natl. Acad. Sci. USA 95: 12906-11.
Schmiesing, J. A., Gregson, H. C., Zhou, S., and Yokomori, K. (2000). A human condensin complex containing hCAP-C/hCAP-E and CNAP1, a homolog of Xenopus XCA-D2, colocalizes with phosphorylated histone H3 during the early stage of mitotic chromosome condensation. Mol. Cell. Biol. 20: 6996-7006.
Ball, A. R., and Yokomori, K. (2001). The structural maintenance of chromosomes (SMC) family of proteins in mammals. Chromosome Res. 9:85-96
Gregson, H. C., Schmiesing, J. A., Kim, J.-S., Ball, A. R., Kobayashi, T., Zhou, S., and Yokomori, K. (2001). A potential role of human cohesin in spindle organization. J. Biol. Chem. 276:47676-47682.
Gregson, H. C., Van Hooser, A., Ball, A. R., Schmiesing, J. A., Brinkley, W., Yokomori, K. (2002). Localization of human SMC1 protein at kinetochores. Chromosome Res. 10: 267-277.
Ball, Jr., A. R., Schmiesing, J. A., Zhou, C., Gregson, H. C., Okada, Y., Doi, T., and Yokomori, K. (2002). Identification of a chromosome-targeting domain in the human condensin subunit CNAP1/hCAP-D2/Eg7. Mol. Cell. Biol. 22:5769-5781.
Hakimi, M.-A., Bochar, D. A., Schmiesing, J. A., Dong, Y., Barak, O. G., Speicher, D. A., Yokomori, K., and Shiekhattar, R. (2002). A chromatin remodeling complex that loads cohesin onto human chromosomes. Nature 418:994-998.
Kim, J.-S., Krasieva, T. B., LaMorte, V., Taylor, A. M. R., and Yokomori, K. (2002). Specific recruitment of human cohesin to laser-induced DNA damage. J. Biol. Chem. 277:45149-45153.
Yokomori, K. (2003). SMC protein complexes and the maintenance of chromosome integrity. Curr. Topics Microbiol. Immunol. "Protein complexes that modify chromatin" 274: 79-112.
Bermudez, V. P., Maniwa, Y., Tappin, I., Ozato, K., Yokomori, K., and Hurwitz, J. (2003). The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA. Proc. Natl. Acad. Sci. 100:1023710242.
Kim, J. S., Krasieva, T. B., Kurumizaka, H., Chen, D. J., Taylor, A. M., Yokomori, K., (2005) Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells. J Cell Biol. 170: 341-7.
Heale, J. A., Ball, Jr., A. R., Schmiesing, J. A., Kim, J.-S., Kong, X., Zhou, S., Hudson, D. F., Eanrshaw, W.C., and Yokomori, K. (2006). Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Molecular Cell 21:837-48.
Kim, J.-S., Heale, J., Zeng, W., Kong, X., and Yokomori, K. (2007). In situ analysis of DNA damage response and repair using laser microirradiation. Methods Cell Biol. 82: 377-407.
Hou, F., Chu, C.-W., Kong, X., Yokomori, K., and Zou, H. (2007). The acetyltransferase activity of San stabilizes the mitotic cohesin at the centromeres in a shugoshin-independent manner. J. Cell Biol. 177: 587-97.
Murakawa, Y., Sonoda, E., Barber, L. J., Boulton, S. J., Zeng, W., Yokomori, K., Kimura, H., Niimi, A., Hochegger, H., Zhao, G. Y., and Takeda, S. (2007). Inhibitors of the proteosome suppress homologous DNA recombination in mammalian cells. Cancer Res. 67: 8536-43.
Ball, Jr., A. R. and Yokomori, K. (2008). Damage-induced reactivation of cohesin in postreplicative DNA repair. BioEssay 30: 5-9.
Parelho, V., Hadjur, S.,m Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., Jarmuz, A., Canzonetta, C., Webster, Z., Nesterova, T., Cobb, B. S., Yokomori, K., Dillon, N., Aragon, L., Fisher, A. G., Merkenschlager, M. (2008). Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132: 422-33.
Kong, X., Ball, Jr., A. R., Sonoda, E., Feng, J., Takeda, S., Fukagawa, T., Yen, T. J., and Yokomori, K. (2009). Cohesin associates with spindle poles in a mitosis-specific manner and functions in spindle assembly in vertebrate cells. Mol. Biol. Cell 20: 1289-301.
Kong, X., Mohanty, S., Stephens, J., Heale, J. T., Gomez-Godinez, V., Shi, L., Kim, J.-S., Yokomori, K.* and Berns, M. W.* (2009). Comparative analysis of different laser systems to study cellular responses to DNA damage in mammalian cells. Nucleci Acid Res. Doi: 10.1093/nar/gkp221. (* equal corresponding authors).
Ball, Jr., A. R. and Yokomori, K. (2009). Revisiting the role of Heterochromatin Protein 1 in DNA repair. J. Cell Biol. 185: 573-5.
Zeng, W., de Greef, J. C., Chen, Y.-Y., Chien, R., Kong, X., Gregson, H. C., Winokur, S. T., Pyle, A., Robertson, K. D., Schmiesing, J. A., Kimonis, V. E., Balog, J., Frants. R. R., Ball, Jr., A. R., Lock, L. F., Donovan, P. J., van der Maarel, S., and Yokomori, K. (2009). Specific loss of histone H3 lysine 9 trimethylation and HP1g/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet. 5:e1000559. Doi: 10.1371/journal.pgen.1000559.
Kawauchi, S., Calof, A. L., Santos, R., Lopez-Burks, M. E., Young, C. M., Hoang, M. P., Chua, A., Lao, T., Lechner, M. S., Daniel, J. A., Nussenzweig, A., Kitzes, L., Yokomori, K., Hallgrimsson, B., Lander, A. D. (2009). Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/- Mouse, a Model of Cornelia de Lange Syndrome. PLoS Genet. 5: e1000650.
Yusufzai, T., Kong, X., Yokomori, K., and Kadonaga, J. T. (2009). The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA. Genes Dev. 23: 2000-4.
Zeng, W., Ball, Jr., A. R., and Yokomori, K. (2010). HP1: heterochromatin binding proteins working the genome. Epigenetics 5: 287-92.
Gomez-Godinez, V., Wu, T., Sherman, A. J., Lee, C. S., Liaw, L. H., Zhongsheng, Y., Yokomori, K., and Berns, M. W. (2010). DNA repair and chromatin structure studied by laser microirradiation of mitotic chromosomes. Nucleic. Acid Res. 38: e202.
Wu, S., Wang, W., Kong, X., Congdon, L. M., Yokomori, K., Kirschner, M. W., and Rice, J. C. (2010). Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev. 24: 2531-42.
Chien, R., Zeng, W., Kawauchi, S., Bender, M. A., Santos, R., Gregson, H. C., Schmiesing, J. A., Newkirk, D. A., Kong, X., Ball, Jr., A. R., Calof, A. L., Lander, A. D., Groudine. M., and Yokomori, K. (2011). Cohesin mediates chromatin interactions that regulate mammalian b-globin expression. J. Biol. Chem. 286: 17870-8.
Ball, Jr., A. R. and Yokomori, K. (2011). Chromatin damage site: open or close? Curr. Opin. Cell Biol. (in press).