Eun Yong
Shim,
Ph.D.
Assistant Professor/Research
Profile and Contact Information |
Research
RESEARCH
Research Program
A hallmark of cancer cells is chromosome instability. Multiple cellular mechanisms have been identified to maintain chromosome integrity and hold keys to novel therapeutics development as well as cancer prevention. In eukaryotic cells, chromosomes are packaged to specific protein-DNA complex called “chromatin”. Chromatin modifications and remodeling have been perceived as a integral part of daily chromosome transactions including chromosomal damage recognition and repair processes. Consistent with this view, defective chromatin remodeling enzymes have been implicated in failure to tolerate genotoxic chemical exposure and tumorigenesis despite lack of sufficient details how chromatin remodeling contributes to chromosome integrity. Our research is primarily focused on how cells modify chromatin in response to DNA double strand breaks. Especially, we investigate the role of the highly abundant and evolutionary conserved chromatin remodeling complex, RSC (PBAF in human) for chromosome integrity in a tractable yeast system.
Selected Publications
- Kim, C.G., Shim, E.Y., Lee J.E., Jang, Y.K., Lee, C.G. and Park, S.D. (1994) Allosteric interaction of a herpes simplex viral thymidine kinase with host DNA polymerase alpha in mouse LP1-1 cells. Biochem. Mol. Biol. Int. 32: 651-657.
- McPherson, C.E., Shim, E.Y., Friedman, D.S. and Zaret, K.S. (1993) An active tissue-specific enhancer and bound transcription factors existing in a precisely positioned nucleosomal array. Cell 75: 385-398.
- Shim, E.Y., Woodcock, C. and Zaret K.S. (1998) Nucleosome positioning by the winged helix transcription factor HNF3. Genes Dev. 12: 5-10.
- Cirillo, L.A., McPherson, C.E., Bossard, P., Stevens, K., Cherian, S., Shim, E.Y., Clark, K.L., Burley, S.K. and Zaret, K.S. (1998) Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome. EMBO J. 17: 244-254.
- Batchelder, C., Dunn, M., Choy, B., Suh, Y., Cassie, C., Shim, E.Y., Shim, T.H., Mello, C., Seydoux, G. and Blackwell, T.K. (1999) Transcriptional repression by the C. elegans germline protein PIE-1. Genes Dev. 13: 202-212.
- *Navarro, R.E., *Shim, E.Y., Kohara, Y., Singson, A. and Blackwell, T.K. (2001) CGH-1: A conserved predicted RNA helicase required for gametogenesis and protection from physiological germline apoptosis in C. elegans. Development 128: 3221-3232. *These two authors contributed equally.
- Shim, E.Y., Walker, A. and Blackwell, T.K. (2002) CDK9/CyclinT (P-TEFb) is required in two postinitiation pathways for transcription in C. elegans embryo. Genes Dev. 16: 2135-2146.
- Shim, E.Y., Walker, A.K. and Blackwell, T.K. (2002) Broad requirement for the mediator subunit RGR-1 for transcription in the Caenorhabditis elegans embryo. J. Biol. Chem. 277: 30413-30416.
- Shim, E.Y., Ma, JL, Oum, JH, Yanez, Y, Lee, SE. (2005) The Yeast Chromatin Remodeler RSC Complex Facilitates End Joining Repair of DNA Double-Strand Breaks. Mol. Cell. Biol. 25:3934-3944.
- Shim, E.Y., Hong, SJ, Oum, JH, Yanez, Y, Zhang, Y, Lee, SE. (2007) RSC mobilizes nucleosomes to improve accessibility of repair machinery to the damaged chromatin. Mol. Cell. Biol. 27: 1602-1613.
- Zhang, Y., Hefferin, M. L., Chen, L. Shim, E. Y., Tseng, H. M., Kwon, Y., Sung, P., Lee, S. E., Tomkinson, A. E. (2007) Role of Dnl4-Lif1in nonhomologous end-joining repair complex assembly and suppression of homologous recombination. Nat. Struc. Mol. Biol. 14: 639-46.
- Zhu, Z., Chung, W. H., Shim, E. Y., Lee, S. E., Ira, G. (2008) Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 134: 981-94.
- Zhang, Y., Shim, E. Y., Davis, M., Lee, S. E. (2009) Regulation of repair choice: Cdk1 suppresses recruitment of End Joining Factors at DNA breaks. DNA Repair (in press).