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Patrick Sung, Ph.D.
Biochemistry and structural biology
Endogenous free radicals and environmental agents such as ionizing radiation induce DNA double-strand breaks. The repair of these breaks is crucial for the maintenance of genome stability. Two distinct pathways help eliminate DNA double-strand breaks. In homologous recombination (HR), the repair of a broken DNA molecule requires an intact homologous duplex to direct the process. Alternatively, a pathway known as non-homologous DNA end joining (NHEJ) simply rejoins the ends of the broken DNA molecule. Our research efforts focus on delineating the mechanism of homology-directed repair of DNA double-strand breaks in the yeast Saccharomyces cerevisiae and in humans, with special emphasis being placed on the roles of the breast and ovarian tumor suppressors BRCA1 and BRCA2 in the repair process.
Related diseases: Breast cancer, ovarian cancer, childhood cancers
Techniques: Protein purification, nucleic acid biochemistry, enzymology, cell biology, single-molecule biophysics, structural biology including cryoEM, EM, AFM, SAXS, NMR, and X-ray crystallography
Publications
Sung, P., L. Prakash, S. W. Matson, and S. Prakash (1987) RAD3 protein of Saccharomyces cerevisiae is a DNA helicase. Proc. Natl. Acad. Sci. USA 84:8951-8955.
Sung, P., V. Bailly, C. Weber, L. H. Thompson, L. Prakash, and S. Prakash. (1993) Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature365:852-855.
Sung P. (1994) Catalysis of ATP-dependent homologous DNA pairing and strand exchange by yeast RAD51 protein. Science 265:1241-1243.
Sung P. and Robberson D. (1995) DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell 82:453-461.
Petukhova G, Stratton S, and Sung P. (1998) Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature 393: 91-94.
Krejci L, Van Komen S, Li Y, Villemain J, Reddy MS, Klein H, Ellenberger T, Sung P. (2003) DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 423:305-9.
Sehorn, M.G. Sigurdsson, S., Bussen, W., Unger, V.M. and Sung, P. (2004) The Human Meiotic Recombinase Dmc1 Promotes ATP-dependent Homologous DNA Strand Exchange. Nature 429:433-37.
Niu, H, Chung, W.H.,Zhu, Z., Kwon, Y.H., Zhao, W.X., Chi, P., Prakash, R. Seong, C.H., Liu, D.Q., Lu, L., Ira, G. and Sung, P. (2010) Mechanism of the ATP-dependent DNA Double-stranded Break Resection Machinery from S. cerevisiae. Nature 467:108-11.
Wilson MA, Kwon Y, Xu Y, Chung WH, Chi P, Niu H, Mayle R, Chen X, Malkova A, *Sung P, Ira G. Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. (2013) Nature 502:393-6.
Qi Z, Redding S, Lee, JS, Gibb B, Kwon YH, Niu HY, Gaines WA, Sung P, and Greene EC. (2014) Mechanism of DNA sequence alignment during homologous recombination Cell 160:856-69.
Lee JY, Terakawa T, Qi Z, Steinfeld JB, Redding S, Kwon Y, Gaines WA, Zhao W, Sung P, and Greene EC. (2015) Base triplet stepping by the Rad51/RecA family of recombinases. Science 349:977-81.
Zhao W, Steinfeld JB, Liang FS, Chen XY, Maranon DG, Ma CJ, Kwon YH, Rao T, Wang WB, Sheng C, Song XM, Deng YH, Jimenez-Sainz J, Lu L, Jensen RB, Xiong Y, Kupfer GM, Wiese C, Greene EC, Sung P. (2017) Promotion of RAD51-mediated homologous DNA pairing by BRCA1-BARD1. Nature 550:360-365.
Crickard JB, Moevus CJ, Kwon Y, Sung P, Greene EC. (2020) Rad54 Drives ATP Hydrolysis-Dependent DNA Sequence Alignment during Homologous Recombination Cell 181:1380-1394.
Grants
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DNA damage response, DNA repair, and tumor suppression
Education
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Education
- 1985 - D. Phil. - Biochemistry - University of Oxford
- 1981 - B.Sc. (honors) - Biochemistry - University of Liverpool, United Kingdom