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Suk-Hee Lee, Ph.D.

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Professor
Member of IU 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 MS0042
Indianapolis, Indiana 46202-5126

Phone: (317) 278-3464
Facsimile: (317) 274-4686
E-mail: slee@iu.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, S-J, Armstrong, SA, Kim, C-H, Robertson, K, Kelley, MM, 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

Lee, S-H, Oshige, M, Durant, S, Nickoloff, J, Rasila, KK, Williamson, E, Ramsey, H, Kwan, L, and Hromas RA (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 SLM, 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 BD, and Lee S-H (2006) A positive involvement of RecQL4 in UV-induced S-phase arrest. DNA & Cell Biol. 25(12): 696-703

Beck BD, Hah D-S, and 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 MM, Hromas RA, 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 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

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

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

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

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 LP, Wray J, Williamson EA, Durant ST, Corwin L, Gentry AC, Osheroff N, Lee S-H, and Hromas H, Nickoloff JA (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 EA, Lee S-H, Nickoloff JA and Hromas R (2010) The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations. Cancer Genetics & Cytogenetics 200(2), 184-190

Fnu S, Williamson EA, De Haro L, Wray J, Brenneman M, Lee S-H, Nickoloff J, and 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, and 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 BD, Saadatzadeh MR, Haneline LS, Clapp DW, and Lee S-H (2011) Fanconi anemia D2 protein is an apoptotic target mediated by caspases. J. Cell. Biochem. 112(9), 2383-2391

Hromas R, Williamson E, Lee Y-J, Park S-J, Beck BD, You J-S, Laitao A, Nickoloff JA, and Lee S-H (2012) Chk1 phosphorylation of Metnase/SETMAR at Ser495 inhibits replication fork recovery but enhances DNA repair. Oncogene 31(38), 4245-4254

Williamson EA, Damiani L, Leitao A, Hu C, Hathaway H, Oprea T, Sklar L, Shaheen M., Bauman J, Wang W, Nickoloff JA, Lee S-H, and Hromas RA (2012) Targeting the Transposase Domain of the DNA Repair Component Metnase to Enhance Chemotherapy. Cancer Res. 72(23), 6200-6208

Wray J, Williamson EA, Singh SB, Wu Y, Cogle CR, Weinstock DM, Zhang Y, Lee SH, Zhou D, Shao L, Hauer-Jensen M, Pathak R, Klimek V, Nickoloff JA, and Hromas R (2013) PARP1 is required for chromosomal translocations. Blood 121(21), 4359-4365

Mohapatra S, Yannone SM, Lee SH, Hromas RA, Akopiants K, Menon V, Ramsden DA, and Povirk LF. (2013) Trimming of damaged 3' overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases.DNA Repair (Amst) 12(6), 422-432

Kim H S, Hromas R, and Lee S-H (2013) Emerging Features of DNA Double-Strand Break Repair in Humans. Chapter 7 in "New Research Directions in DNA Repair", book edited by C. Chen, ISBN 978-953-51-1114-6 (http://dx.doi.org/10.5772/53811)

Kim H-S, Kim S-K, Chen Q, Nickoloff JA, Hromas R, Georgiadis MM, and Lee S-H (2014) The DDN catalytic motif is required for Metnase's functions in NHEJ repair and replication restart. J. Biol. Chem. 289, 10930–10938

Byrne M, Wray J, Reinert B, Wu Y, Nickoloff J, Lee S-H, Hromas R, Williamson E. (2014) Mechanisms of oncogenic chromosomal translocation. Ann N Y Acad Sci. 1310(1), 89-97

Williamson E, Wu Y, Singh S, Byrne M, Lee S-H, Nickoloff JA, Hromas R (2014) The DNA repair component Metnase regulates Chk1 stability. Cell Division 9:1. DOI: 10.1186/1747-1028-9-1

Kim H-S, Guo C, Thompson EL, Jiang Y, Kelley MR, Vasko MR, Lee S-H (2015) APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER. Mutat. Res. 779, 96-104

Wu Y, Lee S-H, Williamson EA, Reinert BL, Jaiswa AS, Srinivasan, Patel B, Zhou D, Shao L, Hauer-Jensen M, Singh S, Kong K, Wu X, Cho JH, Xia F, Kim H-S, Beissbarth T, Gaedcke J, Burma S, Nickoloff JA, and Hromas RA (2015) EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair. PLoS Genet. 11(12): e1005675

Kim H-S, Kim S-K, Hromas R, and Lee S-H (2015) The SET Domain Is Essential for Metnase Functions in Replication Restart and the 5' End of SS-Overhang Cleavage. PLoS ONE 10(10): e0139418

 

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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.  

635 Barnhill Dr | Indianapolis, IN 46202 | Ph: (317) 274-7151 | Fax: (317) 274-4686