Assistant Professor, Biological Chemistry
Kinetochore ensures faithful segregation of sister chromatids during mitosis by connecting centromeric DNA and spindle microtubules. Especially, inner kinetochore components recognize centromeric DNA and build up the platform for kinetochore assembly. Two different types of centromeres, point centromere (budding yeast) and regional centromere (fission yeast to human), have been reported. Genetic and molecular mechanisms of inner kinetochore at point centromere are relatively well studied, but the recruiting mechanism of the centromere-specific nucleosomes at regional centromere and its epigenetic features are not well understood. My laboratory will focus on understanding these processes using structural and biochemical approaches. Especially, I will focus on the centromere-specific nucleosome recruitment mechanisms in fission yeast and human.
Histone chaperones (HCs), such as Asf1, Rtt106, CAF-1, HIRA, and FACT, play important roles in nucleosome assembly during DNA replication and DNA repair. Newly synthesized H3:H4 dimer is captured by Asf1 and acetylated by histone acetyltransferases (histone H3 Lys56). Following acetylation, H3-H4 dimers are handed off to the next set of chaperones, CAF-1 and Rtt106, which proceed to deposit the histones onto nascent DNA. HIRA is responsible for DNA replication independent histone assembly and FACT is involved in nucleosome disassembly and reassembly. Understanding nucleosome assembly mechanisms by its chaperones is a crucial not only to understand how newly synthesized histones are recruited during DNA replication and repair, but also important to reveal transferring mechanism of epigenetic information to newly incorporated nucleosomes. As a long-term goal, I like to propose the structural and biochemical studies of HCs and address questions of: What are structural features of those HCs as it is and as a complex with its substrates, histones? How HCs recognize and stabilize histones in solution? How HCs distinguish histone variants, e.g. histone H3.1 by CAF-1 and histone H3.3 by HIRA? What is the effect of H3 acetylation in transferring histones from Asf1 to either Rtt105 or CAF-1 and eventually nucleosome incorporation?
Current Lab members
- Dr. Hanseong Kim
- Dr. Sojin An
- Justin Kim
- Patrick McCombs
- Michael Gersten
2012 : BSSP (Biological Sciences Scholars Program ) Scholar award, University of Michigan
2010-present: Special Fellowship of the Leukemia & Lymphoma Society
Lee S.J., McCormick M.S., Lippard S.J., and Cho U.S. (2013) Control of Substrate Access to the Active Site in Methane Monooxygenase, Nature, doi: 10.1038/nature11880
Cho, U.S. and Harrison, S.C. (2011) Ndc10 is a platform for inner kinetochore assembly in budding yeast. Nat. Struct. Mol. Biol., doi: 10.1038/nsmb.2178
Cho, U.S. and Harrison, S.C. (2011) Recognition of the centromere-specific histone Cse4 by the chaperone Scm3. Proc. Natl. Acad. Sci. USA, 108(23), 9367-9371
Cho, U.S., Corbett, K.D., Al-Bassam, J., Bellizzi, J.J. 3rd, De Wulf, P., Espelin, C.W., Miranda, J.J., Simons, K., Wei, R.R., Sorger, P.K., Harrison, S.C. (2011) Molecular Structures and Interactions in the Yeast Kinetochore. Cold Spring Harb Symp Quant Biol., 75, 395-401
Xu, Z., Cetin, B., Anger, M., Cho, U.S., Helmhart, W., Nasmyth, K. and Xu, W. (2009) Structure and function of the PP2A-shugoshin interaction. Mol. Cell, 35, 426-441
Cho, U.S., Morrone, S., Sablina, A.A., Arroyo, J.D., Hahn, W.C., Xu, W (2007) Structural basis of PP2A inhibition by small-t antigen. PLoS Biology 5, e202
Cho, U.S. and Xu, W (2007) Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature (Research Article) 445, 53-57
Sampietro J., Dahlberg L. C., Cho, U. S., Hinds R. T., Kimelman D., Xu W. (2006) Crystal Structure of a β-catenin/BCL9/Tcf4 Complex. Mol. Cell. 24, 293-300
Cho, U. S., Bader W. M., Amaya F. M., Daley E. M., Klevit E. R., Miller I. S., and Xu W.(2006) Crystal structure of the PhoQ sensor domain suggests a mechanism for transmembrane signaling. J. Mol. Biol. 356, 1193-1206
* This paper was highlighted in Science Editor's choice (2006) Science 311, 147
Bader M. W., Sanowar S., Daley M. E., Schneider A. R., Cho, U. S., Xu W., Klevit R. E., Le Moual H. and Miller S. I. (2005). Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122, 461-72.
Chan S., Segelke B., Lekin T., Krupka H., Cho, U. S., Kim M. Y., So M., Kim C. Y., Naranjo C. M., Rogers Y. C., Park M. S., Waldo G. S., Pashkov I., Cascio D., Perry J. L. and Sawaya M. R. (2004). Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism. J. Mol. Biol. 341, 503-17.