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Dr. Hung-Yuan (Peter) Chi
Joint Appointment Assistant Research Fellow
Room N203, Institute of Biochemical Sciences, National Taiwan University
No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan
TEL: +886-2-3366-4066
FAX: +886-2-2363-5038
peterhchi@ntu.edu.tw

Our Interests

Our laboratory is interested in deciphering the functional and mechanistic role of homologous recombination in biology.

The Biology of Homologous Recombination

Homologous recombination (HR) governs genomic transactions. It represents a major chromosome repair tool that helps to eliminate deleterious lesions such as DNA double strand breaks (DSBs), mediate the restart of stalled or collapsed DNA replication forks, ensure proper meiotic chromosome segregation, as well as to maintain the length of telomeres in some circumstances (Fig. 1). As such, HR is indispensable for the maintenance of genome integrity. Studies in the past have provided compelling evidence for a tumor suppression role of HR. For instance, cell lines from familial breast cancer patients that harbor mutations in BRCA2 exhibit hypersensitivity to DNA damaging agents and a pronounced deficiency in HR. Aside from its genome maintenance and tumor suppression functions, HR also serves more specialized roles in various organisms, such as mating type switching in the budding yeast and V(D)J recombination in the immune system. In summary HR play an essential role in biology and dysregulation of HR causes severe disease such as cancer.

Homologous Recombination Pathway

HR is often induced via the formation of DSBs, which leads to the nucleolytic processing of DSB ends to generate 3' single-stranded DNA (ssDNA) tails. Herein, the 3' single-stranded tail associates with recombinases to form a nucleoprotein filament, which is then activated to invade a homologous duplex DNA molecule to form a displacement loop or D-loop. The 3' invading strand is extended by DNA synthesis, followed by the pairing of the non-invading 3' single-stranded tail with the homologous ssDNA strand in the enlarging D-loop (second end capture). The now paired second 3' end is also extended by DNA synthesis and subsequent ligations generate a double Holliday Junction (dHJ) intermediate. Resolution of the dHJ intermediate can result in crossover or non-crossover recombinant products (Fig. 2). In summary, the HR pathway is constituted by a sequence of events that involve (1) DSBs formation; (2) end resection to create 3' overhang ssDNA; (3) assembly of recombinase onto ssDNA; (4) D-loop mediated DNA synthesis; and (5) formation & resolution of dHJ intermediate.

2003, 07 - 2007, 12 Ph.D., Molecular Biophysics and Biochemistry, Yale University

2011,10 - present Joint Appointment Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
2010,08 - present Assistant Professor, Institute of Biochemical Sciences, National Taiwan University
2010,02 - 2010,07 Postdoctoral Associate, Yale University
2008,01 - 2010,01 Postdoctoral Fellow, The Rockefeller University

    Publications List
Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1 complex.
Su GC, Chung CI, Liao CY, Lin SW, Tsai CT, Huang T, Li HW, Chi P Nucleic Acids Res. (2014)
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)
Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex.
Tsai SP, Su GC, Lin SW, Chung CI, Xue X, Dunlop MH, Akamatsu Y, Jasin M, Sung P, Chi P Nucleic Acids Res. (2012)
Analyses of the yeast Rad51 recombinase A265V mutant reveal different in vivo roles of Swi2-like factors.
Chi P, Kwon Y, Visnapuu ML, Lam I, Santa Maria SR, Zheng X, Epshtein A, Greene EC, Sung P, Klein HL Nucleic acids research (2011)
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 Nature (2010)
Functional interactions of meiotic recombination factors Rdh54 and Dmc1.
Chi P, Kwon Y, Moses DN, Seong C, Sehorn MG, Singh AK, Tsubouchi H, Greene EC, Klein HL, Sung P DNA repair (2009)
Bipartite stimulatory action of the Hop2-Mnd1 complex on the Rad51 recombinase.
Chi P, San Filippo J, Sehorn MG, Petukhova GV, Sung P Genes & development (2007)
RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments.
Hu Y, Raynard S, Sehorn MG, Lu X, Bussen W, Zheng L, Stark JM, Barnes EL, Chi P, Janscak P, Jasin M, Vogel H, Sung P, Luo G Genes & development (2007)
Roles of ATP binding and ATP hydrolysis in human Rad51 recombinase function.
Chi P, Van Komen S, Sehorn MG, Sigurdsson S, Sung P DNA Repair (Amst) (2006)
Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA.
Chi P, Kwon Y, Seong C, Epshtein A, Lam I, Sung P, Klein HL J. Biol. Chem. (2006)

Updated 2017.03.08

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