Dr. Hung-Yuan (Peter)Chi

Name：Dr. Hung-Yuan (Peter)Chi

Title：Distinguished Professor, Director

Lab Office：IBS N203

Phone：(02)23665573、(02)33664066

Email：peterhchi@ntu.edu.tw

Research：Deciphering the functional and mechanistic role of homologous recombination in biology

Journal Papers

Journal Papers
Degrees and Positions Held
Research
Personal Website

Year	Paper Title
2023	Lee, C.Y., Cheng, W.F., Lin, P.H., Chen, Y.L., Huang, S.H., Lei, K.H., Chang, K.Y., Ko, M.Y., and Chi, P.* (2023) An activity-based functional test for identifying homologous recombination deficiencies across cancer types in real-time. Cell Reports Medicine, doi: 10.1016/j.xcrm.2023.101247. Online ahead of print
2023	Guh, C.L., Lei, K.H., Chen, Y.A., Jiang, Y.Z., Chang, H.Y., Liaw, H., Li, H.W., Yen, H.Y., and Chi, P.* (2023) RAD51 paralogs synergize with RAD51 to protect reversed forks from cellular nucleases. Nucleic Acids Res., gkad856. doi: 10.1093/nar/gkad856. Online ahead of print
2023	Luo, S.C., Yeh, M.C., Lien, Y.H., Yeh, H.Y., Siao, H.L., Tu, I.P., Chi, P., and Ho, M.C. (2023) A RAD51–ADP double filament structure unveils the mechanism of filament dynamics in homologous recombination. Nature Communications, 14, Article number: 4993.
2023	Liu, C.C., Chan, H.R., Su, G.C., Hsieh, Y.Z., Lei, K.H., Kato, T., Yu, T.Y., Kao, Y.W., Cheng, T.H., Chi, P., and Lin, J.J. (2023) Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination. Nucleic Acids Res., 51(9):4398-4414.
2022	Ho, Y.C., Ku, C.S., Tsai, S.S., Shiu, J.L., Jiang, Y.Z., Miriam, H.E., Zhang, H.W., Chen, Y.T., Chiu, W.T., Chang, S.B., Shen, C.H., Myung, K., Chi, P., and Liaw, H. (2022) PARP1 recruits DNA translocases to restrain DNA replication and facilitate DNA repair. PLoS Genet., 13;18(12):e1010545.
2022	Blay, V., Gailiunaite, S., Lee, C. Y., Chang, H. Y., Hupp, T., Houston, D. R., and Chi, P. (2022) Comparison of ATP-binding pockets and discovery of homologous recombination inhibitors. Bioorganic & Medicinal Chemistry, 70:116923.
2021	Lei, K.H., Yang, H.L., Chang, H.Y., Yeh, H.Y., Nguyen, D.D., Lee, T.Y., Lyu, X., Chastain, M., Chai, W., Li, H.W., and Chi, P. (2021) Crosstalk between CST and RPA regulates RAD51 activity during replication stress. Nature Communications, 12(1):6412.
2021	Hinman, A. W., Yeh, H.Y., Roelens, B., Yamaya, K., Woglar, A., Bourbon, H-M. G., Chi, P., and Villeneuve, A.M. (2021) Caenorhabditis elegans DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks. Proc Natl Acad Sci U S A., 118(33):e2109306118.
2021	Chen, W.T., Tseng, H.Y., Jiang, C.L., Lee, C.Y., Chi, P., Chen, L.Y., Lo, K.Y., Wang, I.C., and Lin, F.J. (2021) Elp1 facilitates RAD51-mediated homologous recombination repair via translational regulation. J Biomed Sci., 28(1):81.
2021	Li, W.C., Lee, C.Y., Lan, W.H., Woo, T.T., Liu, H.C., Yeh, H.Y., Chang, H.Y., Chuang, Y.C., Chen, C.Y., Chuang, C.N., Chen, C.L., Hsueh, Y.P., Li, H.W., Chi, P., and Wang, T.F.* (2021) Trichoderma reesei Rad51 tolerates mismatches in hybrid meiosis with diverse genome sequences. Proc Natl Acad Sci U S A., 118(8):e2007192118.
2021	Luo, S.C., Yeh, H.Y., Lan, W.H., Wu, Y.M., Yang, C.H., Chang, H.Y., Su, G.C., Lee, C.Y., Wu, W.J., Li, H.W., Ho, M.C.., Chi, P., and Tsai, M.D.* (2021) Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures. Nature Communications, 12(1):115.
2021	Lyu, X., Lei, K.H., Biak Sang, P., Shiva, O., Chastain, M., Chi, P., and Chai, W. (2021) Human CST complex protects stalled replication forks by directly blocking MRE11 degradation of nascent-strand DNA. EMBO J., 40(2):e103654.
2020	Chang, H.Y., Lee, C.Y., Lu, C.H., Lee, W., Yang, H.L., Yeh, H.Y., Li, H.W., Chi, P. (2020) Microcephaly family protein MCPH1 stabilizes RAD51 filaments, Nucleic Acids Res., In press
2020	Lan, W.H., Lin, S.Y., Kao, C.Y., Chang, W.H., Yeh, H.Y., Chang, H.Y., Chi, P., and Li, H.W. (2020) Rad51 facilitates filament assembly of meiosis-specific Dmc1 recombinase. Proc Natl Acad Sci U S A., 117(21): 11257-11264
2019	Lee, C.-Y., Su, G.-C., Huang, W.-Y., Ko, M.-Y., Yeh, H.-Y., Chang, G.-D., Lin, S.-J., & Chi, P*. (2019) Promotion of homology-directed DNA repair by polyamines, Nature Communications, 10:65
2019	Klein, H.L., .., Chi P, Heyer, W.D., .., Niu, H., and Rothenberg, E. (2019) Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes, Microbial Cell, 6(1): 65–101.
2018	Lu, C.-H., Yeh, H.-Y., Su, G.-C., Ito, K., Kurokawa, Y., Iwasaki, H., Chi, P., & Li, H.-W.* (2018) Swi5-Sfr1 Stimulates Rad51 Recombinase Filament Assembly by Modulating Rad51 Dissociation, Proc. Nat. Acad. Sci. U.S.A., 115(43):E10059-E10068.
2017	Huang, W.Y., Lai, S.F., Chiu, H.Y., Chang, M., Plikus, M., Chan, C.C., Chen, Y.T., Tsao, P.N., Yang, T.L., Lee, H.S., Chi, P., and Lin, S.J. (2017) Mobilizing transit-amplifying cell-derived ectopic progenitors prevents hair loss from chemotherapy or radiation therapy. Cancer Research, 77 (22):6083-6096.
2017	Yeh, H.Y., Lin, S.W., Wu, Y.C., Chan, N.L., and Chi, P*. (2017) Functional characterization of the meiosis-specific DNA double-strand break inducing factor SPO-11 from C. elegans. Scientific Reports, 7(1):2370
2016	Chao, A., Chang, T.C., Lapke, N., Jung, S.M., Chi, P., Chen, C.H., Yang, L.Y., Lin, C.T., Huang, H.J., Chou, H.H., Liou, J.D., Chen, S.J., Wang, T.H., and Lai, C.H. (2016) Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer. Oncotarget, 7(51):85529-41.
2016	Su, G.C., Yeh, H.Y., Lin, S.W., Chung, C.I., Huang, Y.S., Liu, Y.C., Lyu, P.C., and Chi, P*. (2016) Role of the RAD51-SWI5-SFR1 ensemble in homologous recombination. Nucleic Acids Res., 44(13):6242-51.
2015	Chang, H.Y., Liao, C.Y., Su, G.C., Lin, S.W., Wang, H.W., Chi, P. (2015) Functional Relationship of ATP Hydrolysis, Presynaptic Filament Stability, and Homologous DNA Pairing Activity of the Human Meiotic Recombinase DMC1. J Biol Chem., 290(32):19863-73.
2014	Zhao, W., Saro, D., Hammel, M., Kwon, Y., Xu, Y., Rambo, R.P., Williams, G.J., Chi, P., Lu, L., Pezza, R.J., Camerini-Otero, R.D., Tainer, J.A., Wang, H.W., Sung, P. (2014) Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing. Nucleic Acids Res., 42(2):906-17.
2014	Su, G.C., Chung, C.I., Liao, C.Y., Lin, S.W., Tsai, C.T., Huang, T., Li, H.W., Chi, P. (2014) Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1 complex. Nucleic Acids Res., 42(1):349-58.
2013	Wilson, M.A., Kwon, Y., Xu, Y., Chung, W.H., Chi, P., Niu, H., Mayle, R., Chen, X., Malkova, A., Sung, P., Ira, G. (2013) Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. Nature, 502(7471):393-6.
2013	Busygina, V., Gaines, W.A., Xu, Y., Kwon, Y., Williams, G.J., Lin, S.W., Chang, H.Y., Chi, P., Wang, H.W., and Sung, P. (2013) Functional attributes of the Saccharomyces cerevisiae meiotic recombinase Dmc1. DNA Repair (Amst), 12(9):707-12.
2012	Tsai, S.P., Su, G.C., Lin, S.W., Chung, C.I., Xue, X., Dunlop, M.H., Akamatsu, Y., Jasin, M., Sung, P., and Chi, P. (2012) Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex.Nucleic Acids Res., 40 (14):6558-69.
2012	Chen, C.H., Chu, P.C., Lee, L., Lien, H.W., Lin, T.L., Fan, C.C., Chi, P., Huang, C.J., and Chang, M.S. (2012) Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response. PLoS One, e33538.
2011	Chi, P., Kwon, Y., Visnapuu, M.L., Lam, I., Santa Maria, S.R., Zheng, X., Epshtein, A., Greene, E.C., Sung, P., and Klein, H.L. (2011) Analyses of the yeast Rad51 recombinase A265V mutant reveal different in vivo roles of Swi2-like factors. Nucleic Acids Res., 1-12.
2010	Niu, H., Chung, W.H., Zhu, Z., Kwon, Y., Zhao, W., Chi, P., Prakash, P., Seong, C., Liu, D., Lu, L., Ira, G., and Sung, P. (2010) Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature, 467(7311):108-11.
2009	Robertson, R.B., Moses, D.N., Kwon, Y., Chan, P., Chi, P., Klein, H., Sung, P., and Greene, E.C. (2009) Structural transitions within human Rad51 nucleoprotein filaments. PNAS, 106(31):12688-93.
2009	Chi, P., Kwon, Y., Moses, D.N., Seong, C., Sehorn, M.G., Singh, A.K., Tsubouchi, H., Greene, E.C., Klein, H.L., and Sung, P. (2009) Functional interactions of meiotic recombination factors Rdh54 and Dmc1. DNA Repair (Amst), 8(2):279-84.
2009	Robertson, R.B., Moses, D.N., Kwon, Y., Chan, P., Chi, P., Klein, H., Sung, P., and Greene, E.C., (2009) Visualizing the disassembly of S.cerevisiae Rad51 nucleoprotein filaments. J. Mol. Biol., 388(4):703-20.
2008	Seong, C., Sehorn, M.G., Plate, I., Shi, I., Song, B., Chi, P., Mortensen, U., Sung, P., and Krejci, L. (2008) Molecular anatomy of the recombination mediator function of Saccharomyces cerevisiae Rad52. J. Biol. Chem., 283(18):12166-74.
2008	Kwon, Y., Seong, C., Chi, P., Greene, E.C., Klein, H., and Sung, P. (2008) ATP-dependent chromatin remodeling by the Saccharomyces cerevisiae homologous recombination factor Rdh54/Tid1. J. Biol. Chem., 283(16):10445-52.
2007	Hu, Y., Raynard, S., Sehorn, M.G., Lu, X., Bussen, W., Zheng, L., Stark, J.M., Barnes, E.L., Chi, P., Janscak, P., Jasin, M., Vogel, H., Sung, P., and Luo, G. (2007) RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes & Develop., 21(23):3078-84.
2007	Chi, P., San Filippo, J., Sehorn, M.G., Petukhova, G.V., and Sung, P. (2007) Bipartite stimulatory action of the Hop2-Mnd1 complex on the Rad51 recombinase. Genes & Develop., 21(14):1747-57.
2007	Kwon,Y., Chi, P., Roh, D. H., Klein, H., and Sung, P. (2007) Synergistic action of the Saccharomyces cerevisiae homologous recombination factors Rad54 and Rad51 in chromatin remodeling. DNA Repair (Amst), 6(10):1496-506.
2007	Prasad, T.K., Robertson, R.B., Visnapuu, M.L., Chi, P., Sung, P., and Greene, E.C. (2007) A DNA-translocating Snf2 molecular motor: Saccharomyces cerevisiae Rdh54 displays processive translocation and extrudes DNA loops. J. Mol. Biol., 369(4):940-53.
2006	Chi, P., Kwon, Y., Seong, C., Epshtein, A., Lam, I., Sung, P., and Klein, H. L. (2006) Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA. J. Biol. Chem., 281(36):26268-79.
2006	Chi, P., Van Komen, S., Sehorn, M.G., Sigurdsson, S., and Sung, P. (2006) Roles of ATP binding and ATP hydrolysis in human Rad51 recombinase function. DNA Repair (Amst), 5(3): 381-91.
2006	San Filippo, J., Chi, P., Sehorn, M.G., Etchin, J., Krejci, L., and Sung, P. (2006) Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide. J. Biol. Chem., 281 (17):11649-57.
2004	Raschle, M., Van Komen, S., Chi, P., Ellenberger, T., and Sung, P. (2004) Multiple interactions with the Rad51 recombinase govern the homologous recombination function of Rad54. J. Biol.Chem., 279(50):51973-80.

School Name	Department	Degree	Period
Academia Sinica	Institute of Biological Chemistry	oint Appointment Research Fellow	2020 – present
National Taiwan University	Institute of Biochemical Sciences	Professor	2019 – present
Academia Sinica	Institute of Biological Chemistry	Joint Appointment Associate Research Fellow	2018 – 2020
National Taiwan University	Institute of Biochemical Sciences	Associate Professor	2014 – 2019
Academia Sinica	Institute of Biological Chemistry	Joint Appointment Assistant Research Fellow	2011 – 2018
National Taiwan University	Institute of Biochemical Sciences	Assistant Professor	2010 – 2014
Yale University		Postdoctoral Associate	2010 – 2010
The Rockefeller University		Postdoctoral Fellow	2008 – 2010
Yale University	Molecular Biophysics and Biochemistry	Ph.D	2003 – 2007

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.

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