Jung-Hyun Min

Associate Professor

Web Site: Min Group Page


Education:

B.S. (Cum Laude) Seoul National University, 1996; Ph.D. University of Washington, 2000; Postdoctoral Research Associate & Leukemia & Lymphoma Society Special Fellow, Howard Hughes Medical Institute & Memorial Sloan-Kettering Cancer Center, 2001-2008



We seek to understand how DNA damage is repaired in an atomic level using X-ray crystallography and various biochemical and biophysical techniques.

The constituent of our genome, DNA is continuously under attacks from the surrounding, which give rise to a plethora of DNA damage. If the damage is left unrepaired, it can result in mutations in critical genes, which may cause uncontrolled cell growth leading to cancer. Luckily, cells are equipped with intricate networks of proteins that cure the damage. In particular, DNA damage generated by ultraviolet (UV) light and various environmental pollutants is repaired by the nucleotide excision repair (NER) pathway. Defects in this pathway can cause skin cancer and also neurological and developmental abnormalities. We are currently focusing on understanding the detailed mechanisms of damage recognition and subsequent repair in NER.

In particular, the nucleotide excision repair (NER) pathway repairs a broad range of DNA lesions generated by ultraviolet light and various chemicals from the environmental pollutants, and defects in this pathway can cause predisposition to cancer and also neurological and developmental abnormalities. NER proceeds in a stepwise manner by sequentially recruiting multiple factors onto the damage site. The xeroderma pigmentosum C (XPC) protein plays a key role in initiating NER in the global genome by recognizing diverse DNA damage and recruiting the downstream factor, transcription factor TFIIH complex. We are currently focusing on understanding the detailed mechanism of the damage recognition and subsequent repair steps in NER.


Min_Fig1Figure 1. The xeroderma pigmentosum C (XPC) protein plays a key role in initiating NER in global genome by recognizing diverse DNA damage and recruiting the downstream transcription factor TFIIH complex. This figure illustrates an XPC (blue) bound to a UV-damage in DNA (yellow), based on the three-dimensional structures determined by X-ray crystallography (1). XPC recognizes DNA damage by inserting a -hairpin into the DNA double helix and flipping out two base pairs containing the damage. The flipped-out nucleotides on the undamaged strand bind specifically to XPC whereas the damaged nucleotides do not make direct contacts with XPC. The structure suggests how XPC can bind to a wide variety of DNA damage. The diverse chemical structures of DNA damage recognized by XPC are also shown in the background.

SELECTED PUBLICATIONS

* indicate (co-)corresponding authorship.
Velmurugu, Y., Chen, X., Slogoff Sevilla, P., Min, J.H.* & Ansari, A., Twist-open mechanism of DNA damage recognition by Rad4/XPC nucleotide excision repair complex, Proc. Natl. Acad. Sci. USA (2016) In press. http://www.pnas.org/content/early/2016/03/30/1514666113

Shafirovich, V., Kropachev, K., Anderson, T., Liu, Z., Kolbanovskiy, M., Martin, B.D., Sugden, K., Shim, Y., Chen, X., Min, J.H., & Geacintov, N.E., Base and Nucleotide Excision Repair of Oxidatively Generated Guanine Lesions in DNA. Journal of Biological Chemistry 291 (10), 5309-5319 (2016).

Puumalainen, M.R., Ruthemann, P., Min, J.H.*, & Naegeli, H., Xeroderma pigmentosum group C sensor: unprecedented recognition strategy and tight spatiotemporal regulation. Cellular and Molecular Life Sciences 73 (3), 547-566 (2016).

Chen, X., Velmurugu, Y., Zheng, G., Park, B., Shim, Y., Kim, Y., Liu, L., Van Houten, B., He, C., Ansari, A., & Min, J.H.*, Kinetic gating mechanism of DNA damage recognition by Rad4/XPC. Nature Communications 6, 5849 (2015).

Lee, Y.C., Cai, Y., Mu, H., Broyde, S., Amin, S., Chen, X., Min, J.H., & Geacintov, N.E., The relationships between XPC binding to conformationally diverse DNA adducts and their excision by the human NER system: Is there a correlation? DNA Repair (Amst) 19, 55-63 (2014).

Koh-Stenta, X., Joy, J., Poulsen, A., Li, R., Tan, Y., Shim, Y., Min, J.H., Wu, L., Ngo, A., Peng, J., Seetoh, W.G., Cao, J., Wee, J.L., Kwek, P.Z., Hung, A., Lakshmanan, U., Flotow, H., Guccione, E., & Hill, J., Characterization of the histone methyltransferase PRDM9 utilising biochemical, biophysical and chemical biology techniques. Biochemical Journal 461 (2), 323-334 (2014).

Zhang, L., Szulwach, K.E., Hon, G.C., Song, C.X., Park, B., Yu, M., Lu, X., Dai, Q., Wang, X., Street, C.R., Tan, H., Min, J.H., Ren, B., Jin, P., & He, C., Tet-mediated covalent labelling of 5-methylcytosine for its genome-wide detection and sequencing. Nature Communications 4, 1517 (2013).

Krasikova, Y.S., Rechkunova, N.I., Maltseva, E.A., Pestryakov, P.E., Petruseva, I.O., Sugasawa, K., Chen, X., Min, J.H., & Lavrik, O.I., Comparative analysis of interaction of human and yeast DNA damage recognition complexes with damaged DNA in nucleotide excision repair. Journal of Biological Chemistry 288 (15), 10936-10947 (2013).

Krasikova, Y.S., Rechkunova, N.I., Maltseva, E.A., Anarbaev, R.O., Pestryakov, P.E., Sugasawa, K., Min, J.H., & Lavrik, O.I., Human and yeast DNA damage recognition complexes bind with high affinity DNA structures mimicking in size transcription bubble. Journal of Molecular Recognition 26 (12), 653-661 (2013).

Shim, Y., Duan, M.R., Chen, X., Smerdon, M.J., & Min, J.H.*, Polycistronic coexpression and nondenaturing purification of histone octamers. Analytical Biochemistry 427 (2), 190-192 (2012).

Yu, M., Hon, G.C., Szulwach, K.E., Song, C.X., Zhang, L., Kim, A., Li, X., Dai, Q., Shen, Y., Park, B., Min, J.H., Jin, P., Ren, B., & He, C., Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome. Cell 149 (6), 1368-1380 (2012).

Min, J. H. and Pavletich, N. P. Recognition of DNA damage by the Rad4 nucleotide excision repair protein. Nature 449, 570-575 (2007).

Yang, H., Ivan, M., Min, J. H., Kim, W. Y., and Kaelin, W. G., Jr. Analysis of von Hippel-Lindau hereditary cancer syndrome: implications of oxygen sensing. Methods in Enzymology 381, 320-335 (2004).

Min, J. H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., Jr., and Pavletich, N. P. Structure of an HIF-1a-pVHL complex: hydroxyproline recognition in signaling. Science 296, 1886-1889 (2002).

Min, J. H., Wilder, C., Aoki, J., Arai, H., Inoue, K., Paul, L., and Gelb, M. H. Platelet-activating factor acetylhydrolases: broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme. Biochemistry 40, 4539-4549 (2001).

Gelb, M. H., Min, J. H., and Jain, M. K. Do membrane-bound enzymes access their substrates from the membrane or aqueous phase: interfacial versus non-interfacial enzymes. Biochimica Biophysica Acta 1488, 20-27 (2000).

Min, J. H., Jain, M. K., Wilder, C., Paul, L., Apitz-Castro, R., Aspleaf, D. C., and Gelb, M. H. Membrane-bound plasma platelet activating factor acetylhydrolase acts on substrate in the aqueous phase. Biochemistry 38, 12935-12942 (1999).
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Contact Information

Office: 2210A SELE, MC 111
Phone: 312-355-0838
Email: jhmin@uic.edu