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2010.10.12 陈俊杰教授(美国德州大学MD安德森癌症中心)学术报告

时间:2010年09月29日 访问次数:2096

报告题目:DNA damage checkpoints and DNA repair

报告人: Junjie Chen, PhD 

           Professor and Chair, Department of Experimental Radiation Oncology, Division of Radiation Oncology,

           The University of Texas MD AndersonCancerCenter, Houston, TX

主持人: 黄 俊 教 授

时 间: 2010年10月12日(星期二)下午3点

地 点: 医学院综合楼205报告厅

 

Introduction of Speaker: 

'
 
Junjie Chen, PhD


Present Title & Affiliation
Primary Appointment


Professor and Chair, Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

 

The overall goal of his laboratory is to understand the molecular mechanisms underlying genomic instability and tumorigenesis. The maintenance of genomic integrity following DNA damage depends on the coordination of DNA repair with cell cycle checkpoint controls. The integrity of the DNA damage response pathway is crucial for the prevention of neoplastic transformation, as suggested by the fact that many proteins involved in these pathways are tumor suppressors including p53, ATM, Chk2, BRCA1 and BRCA2. His group has discovered and studied many new components involved in DNA damage pathways. Recently, Dr. Chen’s group also ventured into other areas of genomic instability, including mitotic regulation, cellular senescence and aging. He demonstrated a mitotic checkpoint protein Chfr is a tumor suppressor, which controls proper mitotic progression via its regulation of several key mitotic kinases. His lab is also studying a protein deacetylase SIRT1 and its role in aging and tumorigenesis.

 

Education & Training

 

Degree-Granting Education

1993 University of Vermont, Burlington, VT, PHD, Cell and Molecular Biology
1989 Institute of Plant Physiology, Academia SINICA, Shanghai, China, Master's Program, Physiology
1988 Fudan University, Shanghai, China, BS, Genetics/Genetic Engineering

Postgraduate Training

1996-1999 Postdoctoral Fellow, Harvard Medical School, Boston, MA, Dr. David M. Livingston
1994-1996 Postdoctoral Fellow, Harvard Medical School, Boston, MA, Dr. Anindya Dutta
1989-1993 Predoctoral Researcher, University of Vermont, Burlington, VT

 

Experience/Service

Academic Appointments

Professor and Chair, Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7/2009-present

Professor, Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 2006-2009

Associate Professor, Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, 2004-2006

Consultant (tenured), Department of Oncology, Mayo Clinic, Rochester, MN, 2003-2006

Assistant Professor, Molecular Pharmacology and Experimental therapeutics, Mayo Medical School, Rochester, MN, 2001-2003

Assistant Professor, Biochemistry and Molecular Medicine, Mayo Medical School, Mayo Foundation, Rochester, MN, 2000-2003

Senior Associate Consultant, Oncology, Mayo Clinic, Rochester, MN, 1999-2003

Selected Publications

Peer-Reviewed Original Research Articles

1. Liu T, Ghosal G, Yuan J, Chen J, Huang J. FAN1 Acts with FANCI-FANCD2 to Promote DNA Interstrand Cross-Link Repair. Science 329(5992):693-6, 8/6/2010. e-Pub 7/29/2010. PMID: 20671156.
2. Huen MS, Sy SM, Leung KM, Ching YP, Tipoe GL, Man C, Dong S, Chen J. SON is a spliceosome-associated factor required for mitotic progression. Cell Cycle 9(13). e-Pub 7/26/2010. PMID: 20581448.
3. Feng L, Wang J, Chen J. The Lys 63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. e-Pub 7/22/2010. PMID: 20656690.
4. Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell 38(6):864-78, 6/25/2010. PMID: 20620956.
5. Santos MA, Huen MS, Jankovic M, Chen HT, López-Contreras AJ, Klein IA, Wong N, Barbancho JL, Fernandez-Capetillo O, Nussenzweig MC, Chen J, Nussenzweig A. Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. J Exp Med 207(5):973-81, 5/10/2010. e-Pub 4/12/2010. PMCID: PMC2867275.
6. Park G, Gong Z, Chen J, Kim JE. Characterization of the DOT1L network: implications of diverse roles for DOT1L. Protein J 29(3):213-23, 4/2010. PMID: 20431927.
7. Huen MS, Huang J, Leung JW, Sy SM, Leung KM, Ching YP, Tsao SW, Chen J. Regulation of chromatin architecture by the PWWP domain-containing DNA damage-responsive factor EXPAND1/MUM1. Mol Cell 37(6):854-64, 3/26/2010. PMID: 20347427.
8. Richards MW, Leung JW, Roe SM, Li K, Chen J, Bayliss R. A pocket on the surface of the N-terminal BRCT domain of Mcph1 is required to prevent abnormal chromosome condensation. J Mol Biol 395(5):908-15, 2/5/2010. e-Pub 11/17/2009. PMCID: PMC2813331.
9. Gong Z, Kim JE, Leung CC, Glover JN, Chen J. BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Mol Cell 37(3):438-46, 2/12/2010. PMID: 20159562.
10. Huen MS, Sy SM, Chen J. BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol 11(2):138-48, 2/2010. e-Pub 12/23/2009. PMID: 20029420.
11. Yuan J, Chen J. MRE11-RAD50-NBS1 complex dictates DNA repair independent of H2AX. J Biol Chem 285(2):1097-104, 1/8/2010. e-Pub 11/12/2009. PMCID: PMC2801237.
12. Kim JE, Lou Z, Chen J. Interactions between DBC1 and SIRT 1 are deregulated in breast cancer cells. Cell Cycle 8(22):3784-5, 11/15/2009. e-Pub 11/11/2009. PMID: 19855164.
13. Yuan J, Chen J. N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair. J Biol Chem 284(46):31746-52, 11/13/2009. e-Pub 9/16/2009. PMCID: PMC2797245.
14. Yuan J, Ghosal G, Chen J. The annealing helicase HARP protects stalled replication forks. Genes Dev 23(20):2394-9, 10/15/2009. e-Pub 9/30/2009. PMCID: PMC2764499.
15. Fu Z, Regan K, Zhang L, Muders MH, Thibodeau SN, French A, Wu Y, Kaufmann SH, Lingle WL, Chen J, Tindall DJ. Deficiencies in Chfr and Mlh1 synergistically enhance tumor susceptibility in mice. J Clin Invest 119(9):2714-24, 9/2009. e-Pub 8/17/2009. PMCID: PMC2735912.
16. Cao L, Xu X, Bunting SF, Liu J, Wang RH, Cao LL, Wu JJ, Peng TN, Chen J, Nussenzweig A, Deng CX, Finkel T. A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol Cell 35(4):534-41, 8/28/2009. PMID: 19716796.
17. Sy SM, Huen MS, Chen J. MRG15 is a novel PALB2-interacting factor involved in homologous recombination. J Biol Chem 284(32):21127-31, 8/7/2009. e-Pub 6/24/2009. PMCID: PMC2755835.
18. Huang J, Gong Z, Ghosal G, Chen J. SOSS complexes participate in the maintenance of genomic stability. Mol Cell 35(3):384-93, 8/14/2009. PMCID: PMC2756616.
19. Sy SM, Huen MS, Zhu Y, Chen J. PALB2 Regulates Recombinational Repair through Chromatin Association and Oligomerization. J Biol Chem 284(27):18302-10, 7/3/2009. e-Pub 5/7/2009. PMCID: PMC2709360.
20. Maddika S, Sy SM, Chen J. Functional interaction between Chfr and Kif22 controls genomic stability. J Biol Chem 284(19):12998-3003, 5/8/2009. e-Pub 3/25/2009. PMCID: PMC2676032.
21. Huang J, Huen MS, Kim H, Leung CC, Glover JN, Yu X, Chen J. RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat Cell Biol 11(5):592-603, 5/2009. e-Pub 4/26/2009. PMCID: PMC2743127.
22. Sy SM, Huen MS, Chen J. PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proc Natl Acad Sci U S A 106(17):7155-60, 4/28/2009. e-Pub 4/15/2009. PMCID: PMC2678481.
23. Maddika S, Chen J. Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase. Nat Cell Biol 11(4):409-19, 4/2009. e-Pub 3/15/2009. PMCID: PMC2754075.
24. Gong Z, Cho YW, Kim JE, Ge K, Chen J. Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage. J Biol Chem 284(11):7284-93, 3/13/2009. e-Pub 1/5/2009. PMCID: PMC2652327.
25. Feng L, Huang J, Chen J. MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev 23(6):719-28, 3/15/2009. e-Pub 3/4/2009. PMCID: PMC2661609.
26. Wu J, Huen MS, Lu LY, Ye L, Dou Y, Ljungman M, Chen J, Yu X. Histone ubiquitination associates with BRCA1-Dependent DNA Damage Response. Mol Cell Biol 29(3):849-860, 2/2009. e-Pub 11/17/2008. PMCID: PMC2630672.
27. Luo K, Yuan J, Chen J, Lou Z. Topoisomerase IIalpha controls the decatenation checkpoint. Nat Cell Biol 11(2):204-10, 2/2009. e-Pub 12/21/2008. PMCID: PMC2712943.
28. Lu LY, Wood JL, Ye L, Minter-Dykhouse K, Saunders TL, Yu X, Chen J. Aurora A is essential for early embryonic development and tumor suppression. J Biol Chem 283(46):31785-31790, 11/14/2008. e-Pub 9/17/2008. PMCID: PMC2581543.
29. Lu LY, Wood JL, Minter-Dykhouse K, Ye L, Saunders TL, Yu X, Chen J. Polo-like kinase 1 is essential for early embryonic development and tumor suppression. Mol Cell Biol 28(22):6870-6, 11/2008. e-Pub 9/15/2008. PMCID: PMC2573299.
30. Wood JL, Liang Y, Li K, Chen J. Microcephalin/MCPH1 associates with the Condensin II complex to function in homologous recombination repair. J Biol Chem 283(43):29586-92, 10/24/2008. e-Pub 8/21/2008. PMCID: PMC2570891.
31. Huen MS, Huang J, Yuan J, Yamamoto M, Akira S, Ashley C, Xiao W, Chen J. Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol Cell Biol 28(19):6104-12, 10/2008. e-Pub 8/4/2008. PMCID: PMC2547017.
32. Fu Z, Malureanu L, Huang J, Wang W, Li H, van Deursen JM, Tindall DJ, Chen J. Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression. Nat Cell Biol 10(9):1076-82, 9/2008. PMCID: PMC2882053.
33. Wu L, Luo K, Lou Z, Chen J. MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks. Proc Natl Acad Sci U S A 105(32):11200-5, 8/12/2008. e-Pub 8/4/2008. PMCID: PMC2516250.
34. Xu C, Wu L, Cui G, Botuyan MV, Chen J, Mer G. Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites. J Mol Biol 381(2):361-72, 8/29/2008. e-Pub 6/14/2008. PMCID: PMC2574983.
35. Wu L, Beito T, Chen J. Generation and characterization of novel monoclonal antibodies against human aurora-A. Hybridoma (Larchmt) 27(4):313-8, 8/2008. PMID: 18707550.
36. Huang J, Chen J. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene 27(29):4056-64, 7/3/2008. e-Pub 3/10/2008. PMID: 18332868.
37. Minter-Dykhouse K, Ward I, Huen MS, Chen J, Lou Z. Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis. J Cell Biol 181(5):727-35, 6/2/2008. e-Pub 5/26/2008. PMCID: PMC2396806.
38. Huen MS, Sy SM, van Deursen JM, Chen J. Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication. J Biol Chem 283(17):11073-7, 4/25/2008. e-Pub 3/3/2008. PMCID: PMC2431066.
39. Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, Vakoc AL, Kim JE, Chen J, Lazar MA, Blobel GA, Vakoc CR. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Mol Cell Biol 28(8):2825-39, 4/2008. e-Pub 2/19/2008. PMCID: PMC2293113.
40. Kim JE, Chen J, Lou Z. DBC1 is a negative regulator of SIRT1. Nature 451(7178):583-6, 1/31/2008. PMID: 18235501.
41. Xie A, Hartlerode A, Stucki M, Odate S, Puget N, Kwok A, Nagaraju G, Yan C, Alt FW, Chen J, Jackson SP, Scully R. Distinct Roles of Chromatin-Associated Proteins MDC1 and 53BP1 in Mammalian Double-Strand Break Repair. Mol Cell 28(6):1045-1057, 12/28/2007. PMCID: PMC2275782.
42. Kim H, Chen J. c-Myc interacts with TRF1/PIN2 and regulates telomere length. Biochem Biophys Res Commun 362(4):842-7, 11/3/2007. e-Pub 8/22/2007. PMCID: PMC2047600.
43. Wood JL, Singh N, Mer G, Chen J. MCPH1 functions in an H2AX-dependent but MDC1-independent pathway in response to DNA damage. J Biol Chem 282(48):35416-23, 11/30/2007. e-Pub 10/9/2007. PMCID: PMC2128040.
44. Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131(5):901-14, 11/30/2007. e-Pub 11/20/2007. PMCID: PMC2149842.
45. Ahmed EA, van der Vaart A, Barten A, Kal HB, Chen J, Lou Z, Minter-Dykhouse K, Bartkova J, Bartek J, de Boer P, de Rooij DG. Differences in DNA double strand breaks repair in male germ cell types: lessons learned from a differential expression of Mdc1 and 53BP1. DNA Repair (Amst) 6(9):1243-54, 9/2007. e-Pub 3/2007. PMID: 17376750.
46. Kim H, Huang J, Chen J. CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. Nat Struct Mol Biol 14(8):710-5, 8/2007. e-Pub 7/22/2007. PMID: 17643122.
47. Kim H, Chen J, Yu X. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316(5828):1202-5, 5/25/2007. PMID: 17525342.
48. Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127(7):1361-73, 12/29/2006. PMCID: PMC1804291.
49. Ward I, Kim JE, Minn K, Chini CC, Mer G, Chen J. The tandem BRCT domain of 53BP1 is not required for its repair function. J Biol Chem 281(50):38472-7, 12/15/2006. e-Pub 10/16/2006. PMCID: PMC1853281.
50. Chini CC, Chen J. Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function. J Biol Chem 281(44):33276-33282, 11/3/2006. e-Pub 9/8/2006. PMID: 16963448.
51. Huang H, Regan KM, Lou Z, Chen J, Tindall DJ. CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage. Science 314(5797):294-7, 10/13/2006. PMID: 17038621.
52. Lai M, Chen J. The role of Vpr in HIV-1 disease progression is independent of its G2 arrest induction function. Cell Cycle 5(19):2275-80, 10/2006. e-Pub 10/1/2006. PMID: 16969134.
53. Wu X, Dong X, Liu W, Chen J. Characterization of CHEK2 mutations in prostate cancer. Hum Mutat 27(8):742-7, 8/2006. PMID: 16835864.
54. Yu X, Fu S, Lai M, Baer R, Chen J. BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP. Genes Dev 20(13):1721-6, 7/1/2006. PMCID: PMC1522068.
55. Chini CC, Wood J, Chen J. Chk1 is required to maintain claspin stability. Oncogene 25(30):4165-71, 7/13/2006. e-Pub 2/27/2006. PMID: 16501606.
56. Ramiro AR, Jankovic M, Callen E, Difilippantonio S, Chen HT, McBride KM, Eisenreich TR, Chen J, Dickins RA, Lowe SW, Nussenzweig A, Nussenzweig MC. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature 440(7080):105-9, 3/2/2006. e-Pub 1/8/2006. PMID: 16400328.
57. Franco S, Gostissa M, Zha S, Lombard DB, Murphy MM, Zarrin AA, Yan C, Tepsuporn S, Morales JC, Adams MM, Lou Z, Bassing CH, Manis JP, Chen J, Carpenter PB, Alt FW. H2AX prevents DNA breaks from Progressing to Chromosome breaks and Translocations. Mol Cell 21(2):201-214, 1/20/2006. PMID: 16427010.
58. Lou Z, Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, Manis JP, van Deursen J, Nussenzweig A, Paull TT, Alt FW, Chen J. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell 21(2):187-200, 1/20/2006. PMID: 16427009.
59. Lai M, Zimmerman ES, Planelles V, Chen J. Activation of the ATR pathway by human immunodeficiency virus type 1 Vpr involves its direct binding to chromatin in vivo. J Virol 79(24):15443-51, 12/2005. PMCID: PMC1315993.
60. Karnitz LM, Flatten KS, Wagner JM, Loegering D, Hackbarth JS, Arlander SJ, Vroman BT, Thomas MB, Baek YU, Hopkins KM, Lieberman HB, Chen J, Cliby WA, Kaufmann SH. Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. Mol Pharmacol 68(6):1636-44, 12/2005. e-Pub 8/26/2005. PMID: 16126823.
61. Kim JE, McAvoy SA, Smith DI, Chen J. Human TopBP1 ensures genome integrity during normal S phase. Mol Cell Biol 25(24):10907-15, 12/2005. PMCID: PMC1316943.
62. Ward IM, Difilippantonio S, Minn K, Mueller MD, Molina JR, Yu X, Frisk CS, Ried T, Nussenzweig A, Chen J. 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice. Mol Cell Biol 25(22):10079-86, 11/2005. PMCID: PMC1280262.
63. Lou Z, Minter-Dykhouse K, Chen J. BRCA1 participates in DNA decatenation. Nat Struct Mol Biol 12(7):589-93, 7/2005. e-Pub 6/19/2005. PMID: 15965487.
64. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadiñanos J, López-Otín C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z. Genomic instability in laminopathy-based premature aging. Nat Med 11(7):780-785, 7/2005. e-Pub 6/26/2005. PMID: 15980864.
65. Ohashi A, Zdzienicka MZ, Chen J, Couch FJ. Fanconi anemia complementation group D2 (FANCD2) functions independently of BRCA2- and RAD51-associated homologous recombination in response to DNA damage. J Biol Chem 280(15):14877-83, 4/15/2005. e-Pub 1/25/2005. PMID: 15671039.
66. Andersen JL, Zimmerman ES, DeHart JL, Murala S, Ardon O, Blackett J, Chen J, Planelles V. ATR and GADD45alpha mediate HIV-1 Vpr-induced apoptosis. Cell Death Differ 12(4):326-334, 4/2005. PMID: 15650754.
67. Yu X, Minter-Dykhouse K, Malureanu L, Zhao WM, Zhang D, Merkle CJ, Ward IM, Saya H, Fang G, van Deursen J, Chen J. Chfr is required for tumor suppression and Aurora A regulation. Nat Genet 37(4):401-6, 4/2005. e-Pub 3/27/2005. PMID: 15793587.
68. Kim JE, Billadeau DD, Chen J. The tandem BRCT domains of Ect2 are required for both negative and positive regulation of Ect2 in cytokinesis. J Biol Chem 280(7):5733-9, 2/18/2005. e-Pub 11/15/2004. PMID: 15545273.
69. Lou Z, Chen BP, Asaithamby A, Minter-Dykhouse K, Chen DJ, Chen J. MDC1 regulates DNA-PK autophosphorylation in response to DNA damage. J Biol Chem 279(45):46359-62, 11/5/2004. e-Pub 9/17/2004. PMID: 15377652.
70. Yu X, Chen J. DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol Cell Biol 24(21):9478-86, 11/2004. PMCID: PMC522253.
71. Zimmerman ES, Chen J, Andersen JL, Ardon O, Dehart JL, Blackett J, Choudhary SK, Camerini D, Nghiem P, Planelles V. Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and Hus 1 and induces nuclear BRCA1 and gamma-H2AX focus formation. Mol Cell Biol 24(21):9286-9294, 11/2004. PMCID: PMC522272.
72. Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol 166(6):801-813, 9/13/2004. PMCID: PMC2172115.
73. Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G. Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains. Structure 12(7):1137-46, 7/2004. PMID: 15242590.
74. Ward IM, Reina-San-Martin B, Olaru A, Minn K, Tamada K, Lau JS, Cascalho M, Chen L, Nussenzweig A, Livak F, Nussenzweig MC, Chen J. 53BP1 is required for class switch recombination. J Cell Biol 165(4):459-64, 5/24/2004. PMCID: PMC2172356.
75. Ward IM, Minn K, Chen J. UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress. J Biol Chem 279(11):9677-80, 3/12/2004. e-Pub 1/23/2004. PMID: 14742437.
76. Rodriguez M, Yu X, Chen J, Songyang Z. Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. J Biol Chem 278(52):52914-8, 12/26/2003. e-Pub 10/24/2003. PMID: 14578343.
77. Yu X, Chini CC, He M, Mer G, Chen J. The BRCT domain is a phospho-protein binding domain. Science 302(5645):639-42, 10/24/2003. PMID: 14576433.
78. Wu X, Chen J. Autophosphorylation of checkpoint kinase 2 at serine 516 is required for radiation-induced apoptosis. J Biol Chem 278(38):36163-8, 9/19/2003. e-Pub 7/9/2003. PMID: 12855706.
79. Merkle CJ, Karnitz LM, Henry-Sánchez JT, Chen J. Cloning and characterization of hCTF18, hCTF8, and hDCC1. Human homologs of a Saccharomyces cerevisiae complex involved in sister chromatid cohesion establishment. J Biol Chem 278(32):30051-6, 8/8/2003. e-Pub 5/23/2003. PMID: 12766176.
80. Chini CC, Chen J. Human claspin is required for replication checkpoint control. J Biol Chem 278(32):30057-62, 8/8/2003. e-Pub 5/24/2003. PMID: 12766152.
81. Yamane K, Chen J, Kinsella TJ. Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint. Cancer Res 63(12):3049-3053, 6/15/2003. PMID: 12810625.
82. Ward IM, Minn K, Jorda KG, Chen J. Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. J Biol Chem 278(22):19579-82, 5/30/2003. e-Pub 4/15/2003. PMID: 12697768.
83. Lou Z, Chini CC, Minter-Dykhouse K, Chen J. Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. J Biol Chem 278(16):13599-602, 4/18/2003. e-Pub 2/27/2003. PMID: 12611903.
84. Ward IM, Minn K, van Deursen J, Chen J. p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol Cell Biol 23(7):2556-63, 4/2003. PMCID: PMC150747.
85. Lou Z, Minter-Dykhouse K, Wu X, Chen J. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature 421(6926):957-61, 2/27/2003. PMID: 12607004.
86. Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, Carpenter PB, Bonner WM, Chen J, Nussenzweig A. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol 4(12):993-7, 12/2002. PMID: 12447390.
87. Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE. The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity. J Biol Chem 277(10):7849-56, 3/8/2002. e-Pub 12/18/2001. PMID: 11751867.
88. Yamane K, Wu X, Chen J. A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. Mol Cell Biol 22(2):555-66, 1/2002. PMCID: PMC139754.
89. Ward IM, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 276(51):47759-62, 12/21/2001. e-Pub 10/22/2001. PMID: 11673449.
90. Ward IM, Wu X, Chen J. Threonine 68 of Chk2 is phosphorylated at sites of DNA strand breaks. J Biol Chem 276(51):47755-47758, 12/21/2001. e-Pub 10/19/2001. PMID: 11668173.
91. Joukov V, Chen J, Fox EA, Green JB, Livingston DM. Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development. Proc Natl Acad Sci U S A 98(21):12078-83, 10/9/2001. e-Pub 10/2/2001. PMCID: PMC59770.
92. Rappold I, Iwabuchi K, Date T, Chen J. Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways. J Cell Biol 153(3):613-20, 4/30/2001. PMCID: PMC2190566.
93. Wu X, Webster SR, Chen J. Characterization of tumor-associated Chk2 mutations. J Biol Chem 276(4):2971-4, 1/26/2001. e-Pub 10/26/2000. PMID: 11053450.
94. Chen J. ATR is involved in teh Phosphorlyation of BRCA1 following DNA damage. Cancer Res 60(18):5037-5039, 9/15/2000. PMID: 11016625.
95. Wu X, Petrini JH, Heine WF, Weaver DT, Livingston DM, Chen J. Independence of R/M/N focus formation and the presence of intact BRCA1. Science 289(5476):11-11a, 7/7/2000. PMID: 10928918.
96. Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM. Genetic Analysis of BRCA1 function in a defined tumor cell line. Mol Cell 4(6):1093-1099, 12/1999. PMID: 10635334.
97. Chen JJ, Silver D, Cantor S, Livingston DM, Scully R. BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer Res 59(7 Suppl):1752s-1756s, 4/1/1999. PMID: 10197592.
98. Wilson CA, Ramos L, Villaseñor MR, Anders KH, Press MF, Clarke K, Karlan B, Chen JJ, Scully R, Livingston D, Zuch RH, Kanter MH, Cohen S, Calzone FJ, Slamon DJ. Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet 21(2):236-240, 2/1999. PMID: 9988281.
99. Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol Cell 2(3):317-28, 9/1998. PMID: 9774970.
100. Geraghty DS, Sucic HB, Chen J, Pederson DS. Evidence that partial unwrapping of DNA from nucleosomes facilitates the binding of heat shock factor following DNA replication in yeast. J Biol Chem 273(32):20463-72, 8/7/1998. PMID: 9685401.
101. Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A. Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase. Mol Cell Biol 18(5):2758-67, 5/1998. PMCID: PMC110655.
102. Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM. Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Cell 90(3):425-35, 8/8/1997. PMID: 9267023.
103. Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88(2):265-75, 1/24/1997. PMID: 9008167.
104. Chen U, Chen S, Saha P, Dutta A. p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex. Proc Natl Acad Sci U S A 93(21):11597-602, 10/15/1996. PMCID: PMC38103.
105. Chen J, Saha P, Kornbluth S, Dynlacht BD, Dutta A. Cyclin-binding motifs are essential for the function of p21CIP1. Mol Cell Biol 16(9):4673-82, 9/1996. PMCID: PMC231467.
106. Leiter LM, Chen J, Marathe T, Tanaka M, Dutta A. Loss of transactivation and transrepression function, and not RPA binding, alters growth suppression by p53. Oncogene 12(12):2661-8, 6/20/1996. PMID: 8700525.
107. Chen J, Peters R, Saha P, Lee P, Theodoras A, Pagano M, Wagner G, Dutta A. A 39 amino acid fragment of the cell cycle regulator p21 is sufficient to bind PCNA and partially inhibit DNA replication in vivo. Nucleic Acids Res 24(9):1727-33, 5/1/1996. PMCID: PMC145832.
108. Chen J, Jackson PK, Kirschner MW, Dutta A. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 374(6520):386-8, 3/23/1995. PMID: 7885482.
109. Chen J, Ding M, Pederson DS. Binding of TFIID to the CYC1 TATA boxes in yeast occurs independently of upstream activating sequences. Proc Natl Acad Sci U S A 91(25):11909-13, 12/6/1994. PMCID: PMC45345.
110. Chen J, Pederson DS. A distal heat shock element promotes the rapid response to heat shock of the HSP26 gene in the yeast Saccharomyces cerevisiae. J Biol Chem 268(10):7442-8, 4/5/1993. PMID: 8463277.

Invited Articles

1. Huen MS, Chen J. When loose ends finally meet. Nat Struct Mol Biol 15(12):1241-1242, 12/2008. PMID: 19050718.
2. Wood JL, Chen J. DNA-damage checkpoints: location, location, location. Trends Cell Biol 18(10):451-455, 10/2008. e-Pub 8/27/2008. PMID: 18760607.
3. Kim H, Chen J. New players in the BRCA1-mediated DNA damage responsive pathway. Mol Cells 25(4):457-461, 6/30/2008. e-Pub 4/24/2008. PMID: 18443409.
4. Huen MS, Chen J. The DNA damage response pathways: at the crossroad of protein modifications. Cell Res 18(1):8-16, 1/2008. PMID: 18087291.
5. Lou Z, Chen J. Cellular senescence and DNA repair. Exp Cell Res 312(14):2641-2646, 8/15/2006. e-Pub 6/20/2006. PMID: 16893723.
6. Kim JE, Minter-Dykhouse K, Chen J. Signaling networks controlled by the MRN complex and MDC1 during early DNA damage responses. Mol Carcinog 45(i6):403-408, 6/2006. PMID: 16691596.
7. Baker DJ, Chen J, van Deursen JM. The mitotic checkpoint i cancer and aging: what have mice taught us? Curr Opin Cell Biol 17(6):583-589, 12/2005. e-Pub 10/13/2005. PMID: 16226453.
8. Chini CC, Chen J. Claspin, a regulator of Chk1 in DNA replication stress pathway. DNA Repair (Amst) 3(8-9):1033-1037, Aug-Sep, 8/2004. PMID: 15279790.
9. Ward I, Chen J. Early events in the DNA damage response. Curr Top Dev Biol 63:1-35, 2004. PMID: 15536012.
10. Lou Z, Chen J. Use of siRNA to study the function of MDC1 in DNA damage responses. Methods Mol Biol 281:179-187, 2004. PMID: 15220529.
11. Lou Z, Chen J. BRCA proteins and DNA damage checkpoints. Front Biosci 8:s718-721, 5/1/2003. PMID: 12700125.
Other Articles
1. Huen MS, Chen J. Assembly of checkpoint and repair machineries at DNA damage sites. Trends Biochem Sci 35(2):101-8, 2/2010. e-Pub 10/28/2009. PMID: 19875294.
2. Ande SR, Chen J, Maddika S. The ubiquitin pathway: an emerging drug target in cancer therapy. Eur J Pharmacol 625(1-3):199-205, 12/2009. e-Pub 10/2009. PMID: 19835866.
3. Kim JE, Chen J, Lou Z. p30 DBC is a potential regulator of tumorigenesis. Cell Cycle 8(18):2932-5, 9/2009. e-Pub 9/2009. PMCID: PMC2777512.

Book Chapters

1. Lou ZK, chen JJ. Genome instability in cancer development. In: Advances in Experimental Medicine and Biology. 571. Ed(s) Nigg EA. Springer: New York, 425-455, 2005.  
2. Lou Z, Chen J. Mammalian DNA damage response pathway. In: Adv Exp Med Biol. 570, 425-55, 2005. PMID: 18727510.  

 

 

 

Last updated: 8/27/2010