Patrick Sung, DPhil

Professor of Molecular Biophysics and Biochemistry, and of Therapeutic Radiology and of Epidemiology

Research Interests

Biochemistry; Biophysics; DNA Repair; Radiation Oncology; Homologous Recombination; DNA End-Joining Repair

Research Organizations

Molecular Biophysics and Biochemistry: Sung Lab

School of Public Health

Therapeutic Radiology: Radiobiology

Radiobiology and Radiotherapy

Yale Cancer Center: Radiobiology & Radiotherapy

Office of Cooperative Research

Research Summary

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, 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 mechanisms of homologous recombination.

The recombinational repair of DNA double-strand breaks is mediated by a group of genes called the RAD52 epistasis group. In mammals, the efficiency of recombinational DNA repair is modulated by the tumor suppressors BRCA1, BARD1, BRCA2, PALB2, and BLM, providing compelling evidence that this repair pathway functions to suppress cancer formation. Importantly, recombinational DNA repair is also required for the removal of interstrand DNA crosslinks induced by bifunctional crosslinking agents, which are commonly used to treat various malignancies. In 1994, we identified the yeast Rad51 protein, a key member of the RAD52 group, as the recombinase that mediates the “homologous DNA pairing and strand exchange “reaction central to all recombination-dependent processes, including the repair of DNA double-strand breaks. This finding marked the beginning of studies on recombination enzymology in eukaryotic organisms and has created a much-needed experimental framework for dissecting the role of the other RAD52 group members in the recombination reaction.

Specialized Terms: Repair of DNA double-strand breaks; Repair by homologous recombination; Repair by DNA end-joining

Selected Publications

  • Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2.

    Dray E, Etchin J, Wiese C, Saro D, Williams GJ, Hammel M, Yu X, Galkin VE, Liu D, Tsai MS, Sy SM, Schild D, Egelman E, Chen J, Sung P. Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2. Nature Structural & Molecular Biology 2010, 17:1255-9.

  • Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange.

    Sehorn MG, Sigurdsson S, Bussen W, Unger VM, Sung P. Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange. Nature 2004, 429:433-7.

  • Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration Wilson MA, Kwon Y, Xu Y, Chung WH, Chi P, Niu H, Mayle R, Chen X, Malkova A, Sung P, Ira G. Nature. 2013 Oct 17;502(7471):393-6.
  • Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W, Chi P, Prakash R, Seong C, Liu D, Lu L, Ira G, Sung P. Send to Nature. 2010 Sep 2;467(7311):108-11.
  • Base triplet stepping by the Rad51/RecA family of recombinases Lee JY, Terakawa T, Qi Z, Steinfeld JB, Redding S, Kwon Y, Gaines WA, Zhao W, Sung P, Greene EC. Science. 2015 Aug 28;349(6251):977-81.
  • Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry Zhao W, Vaithiyalingam S, San Filippo J, Maranon DG, Jimenez-Sainz J, Fontenay GV, Kwon Y, Leung SG, Lu L, Jensen RB, Chazin WJ, Wiese C, Sung P. Mol Cell. 2015 Jul 16;59(2):176-87.
  • BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing Zhao W, Steinfeld JB, Liang F, Chen X, Maranon DG, Jian Ma C, Kwon Y, Rao T, Wang W, Sheng C, Song X, Deng Y, Jimenez-Sainz J, Lu L, Jensen RB, Xiong Y, Kupfer GM, Wiese C, Greene EC, Sung P. Nature. 2017 Oct 19;550(7676):360-365.

Full List of PubMed Publications

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