Professor
Member of I.U. Simon Cancer Center

Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
John D. Van Nuys Medical Science Building
635 Barnhill Drive, Room MS0051A
Indianapolis, Indiana 46202-5126

Phone: (317) 278-3464
Facsimile: (317) 274-4686
E-mail: slee@iupui.edu

B.S., 1977, Seoul National University, Seoul, Korea
M.S., 1980, Korea Advanced Institute of Science & Technology, Seoul, Korea
Ph.D., 1987, University of Texas, Austin, TX, USA
Post Doctoral, 1991, Sloan-Kettering Cancer Institute, New York, NY, USA

Area of Study

Molecular mechanism of non-homologous end joining repair in humans; Recognition of cisplatin-induced DNA damage in the early stage of nucleotide excision repair.  More details...

Selected Recent Publications

Park, J-S, Wang, M., Park, S-J, and Lee, S-H. (1999) Zinc finger of RPA, a non-DNA binding element, regulates its DNA binding activity through redox. J. Biol. Chem. 274, 29075-29080.

Park, J-S., Wang, M., Park, S-J., and Lee, S-H. (1999) Involvement of DNA-dependent protein kinase in UV-induced replication arrest. J. Biol. Chem. 274, 32520-32527.

Wang, M., Mahrenholz, A., and Lee, S-H. (2000) RPA stabilizes the XPA-damaged DNA complex through protein-protein interaction. Biochemistry 39 (21), 6433-6439.

You, J-S, Wang, M., and Lee, S-H. (2000) Functional characterization of zinc-finger motif in redox regulation of RPA-ssDNA interaction. Biochemistry 39(42), 12953-12958.

Wang, M., Park, J-S, Ishiai, M., Hurwitz, J., and Lee, S-H (2000) Species-specificity of human RPA in DNA replication lies on RNA primer synthesis Nucl. Acids Res. 28 (23) 4742-4749.

Parker, A., Gu, Y, Mahoney, W., Lee, S-H, Singh, K.K., and Lu, A-L (2001) Human homolog of the MutY repair protein (hMYH) physically interacts with long-patch DNA base excision repair. J. Biol. Chem. 276, 5547-5555.

Lee, S-H. and Maret, W. (2001) Redox control of zinc finger protein: Mechanisms and role in gene regulation Antiox. & Redox Signaling 3(4), 531-534.

Wang, M, You, J-S, and Lee, S-H. (2001) A structure-function analysis of RPA’s zinc finger in redox control. Redox control of zinc finger protein: Mechanisms and role in gene regulation Antiox. & Redox Signaling, 3(4), 657-669.

Park, S-J., Oh, E-J., Yoo, M-A, and Lee, S-H. (2001) Involvement of DNA-dependent protein kinase in regulation of stress-iInduced JNK activation. DNA & Cell Biol. 20 (10), 637-645.

Lee, S-H. (2001) Recognition of DNA Damage in Mammals. J. Biochem. & Mol. Biol. 34 (6), 489-495.

Lee, S-H. and Kim, C-H. (2002) DNA-Dependent Protein Kinase Complex: a Multifunctional Protein in DNA Repair and Damage Checkpoint. Mol. Cells 13(2), 159-166.

Kim, C-H, Park, S-J, and Lee, S-H (2002) Targeted inhibition of Ku70/Ku80 and DNA-PKcs interaction sensitizes breast cancer cells following ionizing radiation. J. Pharm. Exp. Ther. 303 (2), 753-759.

Jeong, H-S, Jeong, I-C, Kim, A, Kang, S-W, Kang, H-S, Kim, Y-J, Lee, S-H, Park, J-S (2002) Cloning of the Large Subunit of Replication Protein A (RPA) from Yeast Saccharomyces cerevisiae and Its DNA Binding Activity through Redox Potential. J. Biochem. Mol. Biol. 35(2):194-198.

Haneline, L.S., Li, X., Ciccone, S., Hong, P., Lee, S-H., Orazi, A., Srour, E.F., and Clapp, D.W. (2003) Retroviral mediated expression of recombinant Fancc enhances the repopulating ability of Fancc-/- hematopoietic stem cells and decreases the risk of clonal evolution. Blood 101(4), 1299-1307.

You, J-S, Wang, M, and Lee, S-H. (2003) Biochemical analysis of damage recognition process in nucleotide excision repair. J. Biol. Chem. 278, 7476-7485.

Freie, BA, Ciccone, S., Li, XX, Niwa, K., Drury, K., Plett, P.A., Orschell-Traycoff, C.M., Srour, E.F., Vogelweid, C., Schantz, L., Hannenberg, H., Lee, S-H, and Clapp, DW (2003) Fanconi Anemia Type C and p53 Cooperate in Cell Cycle Control, Tumorigenesis, and Development. Blood 102: 4146-4152.

Park, S-J., Ciccone, S., Freie, BA., Kurimasa, A, Chen, DJ., Li, GC., Clapp, DW., and Lee, S-H. (2004) A positive role for the Ku complex in DNA replication following strand break damage in mammals. J. Biol. Chem. 279: 6046-6055.

Park, S.-J., Ciccone, S. L. M., Beck, Brian D., Hwang, B., Freie, B., Clapp, D. W., and Lee , S.-H. (2004) Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins J. Biol. Chem. 279: 30053-30059.

Freie, B.W., Ciccone, S., Li, X., Plett, P.A., Orschell-Traycoff, C.M., Srour, E.F., Hannenberg, H., Lee, S-H, and Clapp, D.W. (2004) A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint.J. Biol. Chem. 279(49): 50986-50993.

Park, S-J., Armstrong, S. A., Kim, C.-H., Robertson, K., Kelley, M. M., and Lee S.-H. (2005) Lack of EGF receptor contributes to the drug sensitivity in human germline cells. British J. Cancer 92(2): 334-341.

Young-Ju Lee, Su-Jung Park, Samantha L.M. Ciccone, Chong-Rak Kim, and Suk-Hee Lee (2005) An in vivo analysis of MMC-induced DNA damage and its repair. Carcinogenesis (in press, online published)

Lee, S.-H., Oshige, M., Durant, S., Nickoloff, J., Rasila, K. K., Williamson, E., Ramsey, H., Kwan, L., and Hromas R. A. (2005) The SET domain protein Metnase mediates foreign DNA integration and links integration to NHEJ repair. Proc. Natl. Acad. Sci. USA. 102 (50): 18075-18080.

Lee, Y-J., Park, S-J., Ciccone, S.L.M., Kim, C-R., and Lee S-H. (2006) An in vivo analysis of MMC-induced DNA damage and its repair. Carcinogenesis 27(3): 446-453. 

Park, S-J, Lee, Y-J, Beck, B. D, and Lee S-H (2006) A positive involvement of RecQL4 in UV-induced S-phase arrest. DNA & Cell Biol.  25(12): 696-703.

Beck, B. D., Hah, D-S, Lee, S-H (2007) Molecular mechanisms of Xeroderma Pigmentosum: XPB and XPD between transcription and DNA Repair (Edited by S. Ahmad & F. Hanaoka) Advances in Experimental Medicine & Biology, Landes Biosciences, Springer-Verlag, 637, Chapter 5, 39-46.

Roman, Y., Oshige, M., Lee, Y.-J., Goodwin, K., Georgiadis, M. M., Hromas, R. A., and Lee, S.-H. (2007) Biochemical characterization of a SET and transposase fusion protein, Metnase for its DNA binding and DNA cleavage activity. Biochemistry 46, 11369-11376.

Beck, BD, Park, S-J, Lee Y-J, Roman Y, Hromas R. and Lee S-H (2008). Human Pso4 is a Metnase (SETMAR) binding partner that modulates Metnase-DNA interaction, J. Biol. Chem. 283, 9023-9030.

Williamson EA, Rasila KK, Corwin LK, Wray J, Beck BD, Severns V, Mobarak C, Lee S-H, Nickoloff JA, and Hromas RA (2008). The SET and transposase domain protein Metnase enhances chromosome decatenation: Regulation by Metnase Automethylation. Nucl. Acids Res. 36(18), 5822-5831.

Hromas RA, Wray J, Lee S-H, Leah M, Farrington J, Corwin LK, Ramsey H, Nickoloff JA, and Williamson EA (2008). The human SET and Transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end joining. DNA Repair, 7(12), 1927-1937. Blood 114(9), 1852-1858.

Williamson EA, Farrington J, Martinez L, Ness S, O'Rourke J, Lee S-H, Nickoloff J, and Hromas R (2008). Expression levels of the human DNA repair protein Metnase influence lentiviral genomic integration. Biochimie 90(9), 1422-1426.

Hromas, R, Wray J, Lee S-H, Leah M, Farrington J, Corwin LK, Ramsey H, Nickoloff JA and Williamson EA (2008). The human SET and Transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end joining. DNA Repair 7(12), 1927-1937.

Wray J, Williamson EA, Royce M, Shaheen M, Beck BD, Lee S-H, Nickoloff JA and Hromas R. (2009). Metnase mediates resistance to topoisomerase II inhibitors in breast cancer cells.  PLoS One 4(4), e5323. (Abstract)

Wray J, Williamson EA, Sheema S, Lee S-H, Libby E, Willman CL, Nickoloff JA and Hromas R. (2009) Metnase mediates chromosome decatenation in acute leukemia cells.  Blood 114(9), 1852-1858. (Abstract)

Shaheen M., Williamson E., Nickoloff J., Lee S-H and Hromas R. (2010) Metnase (SETMAR): A Domesticated Primate Transposase that Enhances DNA Repair and Decatenation. Genetica 138(5), 559-566.

Beck BD, Lee SS, Hromas RA, and Lee S-H (2010) Metnase Binding Partner hPso4 negatively Regulates the Metnase' TIR-Specific DNA Binding Activity. Archive. Biophys. Biochem. 498(2), 89-94.

De Haro, L.P, Wray, J., Williamson, E.A., Durant, S.T., Corwin, L., Gentry, A.C., Osheroff, N., Lee S-H and Hromas, H., Nickoloff, J.A. (2010) Metnase promotes replication fork restart after replication stress. Nucl. Acids. Res. 38(17), 5681-5691.  

Goodwin, C, He, H, Imasaki, T, Lee S-H and Georgiadis, MM (2010) Crystal structure of the human Hsmar1-derived transposase domain in the DNA repair enzyme Metnase. Biochemistry 49(27), 5705-5713.

Wray J., Williamson E.A, Lee S-H, Nickoloff J.A and Hromas R. (2010) The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations. Cancer Genetics & Cytogenetics 200(2), 184-190.

Fnu, S., Williamson, E.A., De Haro, L., Wray, J., Brenneman, M., Lee, S-H, Nickoloff, J., Hromas, R. (2011) A histone code for non-homologous end joining DNA repair. Proc. Natl. Acad. Sci. U.S.A. 108, 540-545.

Beck, B., Lee, S-S, Williamson, E., Hromas, R., Lee, S-H (2011) Biochemical characterization of Metnase's endonuclease activity and its role in NHEJ repair. Biochemistry 50(20), 4360-4370.

Park, S-J, Beck, B.D, Saadatzadeh, M.R, Haneline, L.S, Clapp, D.W, Lee, S-H (2011) Fanconi anemia D2 protein is an apoptotic target mediated by caspases. J. Cell. Biochem. doi: 10.1002/jcb.23161. [Epub ahead of print]

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Research Interests

The human genome is littered with sequences derived fromtransposable elements from the Hsmar1 transposon, but there is only one intact copy of the Hsmar1 transposase gene termed Metnase (also known as SETMAR) that exists within a chimeric SET-transposase fusion protein. Although Metnase retains most of the transposase activities, it has evolved as a double-strand break (DSB) repair protein in anthropoid primates. Metnase is localized on chromosome 3p26, a region of frequent abnormalities in various cancers and is highly expressed in most tissues and cell lines. Mutations in Metnase that cause early termination were found in many transformed cell lines, although clinical relevance of these mutations has not been established. Our long-term goal is to understand how a protein with transposase activity in humans promotes DSB repair and chromosome decatenation, and what role the SET domain may play. Given that Metnase requires both the SET and transposase domains for its function(s) in DSB repair, we hypothesize that the acquisition of new functions may have resulted from a chimeric fusion between transposase and the SET domains. Our ongoing study is to elucidate the mechanism of this human SET-transposase protein in DSB repair and chromosome decatenation.

My lab is also interested in cisplatin damage and its repair in humans. Cisplatin is a widely used anti-cancer chemotherapeutic drug that induces DNA damage by forming cisplatin-DNA adducts in cells.  In vivo and in vitro studies strongly suggest that most of the cisplatin-DNA adducts are repaired through nucleotide excision repair (NER) pathway. Due to extensive efforts, we now know a great deal about the mechanism of NER. Recognition of DNA damage is a critical step in the early stage of repair. Xeroderma pigmentosum group A complementing protein (XPA), replication protein A (RPA), XPC-hHR23B, and XPE can independently bind to damaged DNA. However, it is still in debate how the damage recognition proteins function at the damaged DNA site. We use biochemical and molecular approaches to analyze the role(s) of damage recognition proteins in the early stage of DNA repair. We are particularly interested in structural distortion of cisplatin-damaged DNA, a step essential for dual incision, but poorly understood.