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Research topics

Molecular mechanisms of DNA damage response, cell cycle control, oncogenesis, cellular senescence and ageing.

Current Grant Support

2008-2010 GACR 301/08/0353, Protein modifications in DNA damage signalling: Mechanisms and cancer relevance
2008-2012 GACR 204/08/1418, The role of the JAK/STAT signalling pathway in cellular senescence
2009-2011 FP7-HEALTH-2007-2.1.2-5 TRIREME Systems-Level, Multi-layer Understanding of Cellular Responses to Ionizing Radiation
2010-2012 GACR P305/10/P420, Role of Wip1 phosphatase in the DNA damage response

Most important recent papers

(2004-present; names of the lab members underlined)

Lukas C, Melander F, Stucki M, Falck J, Bekker-Jensen S, Goldberg M, Lerenthal Y, Jackson SP, Bartek J, Lukas J. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J 23(13): 2674-83, 2004. (Pubmed) (DOI)

Sorensen CS, Hansen LT, Dziegielewski J, Syljuasen RG, Lundin C, Bartek J, Helleday T. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 7(2): 195-201, 2005. (Pubmed) (DOI)

Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434(7035): 864-70, 2005. (Pubmed) (DOI)

Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, Jackson SP. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8(1): 37-45, 2006. (Pubmed) (DOI)

Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz DC, Lukas J, Bekker-Jensen S, Bartek J, Shiloh Y. Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol 8(8): 870-6, 2006. (Pubmed) (DOI)

Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, Takaoka M, Nakagawa H, Tort F, Fugger K, Johansson F, Sehested M, Andersen CL, Dyrskjot L, Orntoft T, Lukas J, Kittas C, Helleday T, Halazonetis TD, Bartek J, Gorgoulis VG. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444(7119): 633-7, 2006. (Pubmed) (DOI)

Vlasakova J, Novakova Z, Rossmeislova L, Kahle M, Hozak P, Hodny Z. Histone deacetylase inhibitors suppress IFNalpha-induced up-regulation of promyelocytic leukemia protein. Blood 109(4): 1373-80, 2007. (Pubmed) (DOI)

Janderova-Rossmeislova L, Novakova Z, Vlasakova J, Philimonenko V, Hozak P, Hodny Z. PML protein association with specific nucleolar structures differs in normal, tumor and senescent human cells. J Struct Biol 159(1): 56-70, 2007. (Pubmed) (DOI)

Blazkova H, von Schubert C, Mikule K, Schwab R, Angliker N, Schmuckli-Maurer J, Fernandez PC, Doxsey S, Dobbelaere DA. The IKK inhibitor BMS-345541 affects multiple mitotic cell cycle transitions. Cell Cycle 6(20): 2531-40, 2007. (Pubmed)

Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP. Human CtIP promotes DNA end resection. Nature 450(7169): 509-14, 2007. (Pubmed) (DOI)

Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131(5): 887-900, 2007. (Pubmed) (DOI)

Fagerholm R, Hofstetter B, Tommiska J, Aaltonen K, Vrtel R, Syrjakoski K, Kallioniemi A, Kilpivaara O, Mannermaa A, Kosma VM, Uusitupa M, Eskelinen M, Kataja V, Aittomaki K, von Smitten K, Heikkila P, Lukas J, Holli K, Bartkova J, Blomqvist C, Bartek J, Nevanlinna H. NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nat Genet 40(7): 844-53, 2008. (Pubmed) (DOI)

Macurek L, Lindqvist A, Lim D, Lampson MA, Klompmaker R, Freire R, Clouin C, Taylor SS, Yaffe MB, Medema RH. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature 455(7209): 119-23, 2008. (Pubmed) (DOI)

Tanenbaum ME, Macurek L, Galjart N, Medema RH. Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. EMBO J 27(24): 3235-45, 2008. (Pubmed) (DOI)

Rendtlew Danielsen JM, Larsen DH, Schou KB, Freire R, Falck J, Bartek J, Lukas J. HCLK2 is required for activity of the DNA damage response kinase ATR. J Biol Chem 284(7): 4140-7, 2009. (Pubmed) (DOI)

Faustrup H, Bekker-Jensen S, Bartek J, Lukas J, Mailand N. USP7 counteracts SCFbetaTrCP- but not APCCdh1-mediated proteolysis of Claspin. J Cell Biol 184(1): 13-9, 2009. (Pubmed) (DOI)

Carson CT, Orazio NI, Lee DV, Suh J, Bekker-Jensen S, Araujo FD, Lakdawala SS, Lilley CE, Bartek J, Lukas J, Weitzman MD. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection. EMBO J 28(6): 652-62, 2009. (Pubmed) (DOI)

Doil C, Mailand N, Bekker-Jensen S, Menard P, Larsen DH, Pepperkok R, Ellenberg J, Panier S, Durocher D, Bartek J, Lukas J, Lukas C. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136(3): 435-46, 2009. (Pubmed) (DOI)

Liontos M, Niforou K, Velimezi G, Vougas K, Evangelou K, Apostolopoulou K, Vrtel R, Damalas A, Kontovazenitis P, Kotsinas A, Zoumpourlis V, Tsangaris GT, Kittas C, Ginsberg D, Halazonetis TD, Bartek J, Gorgoulis VG. Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas. Am J Pathol 175(1): 376-91, 2009. (Pubmed) (DOI)

Tibelius A, Marhold J, Zentgraf H, Heilig CE, Neitzel H, Ducommun B, Rauch A, Ho AD, Bartek J, Kramer A. Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1. J Cell Biol 185(7): 1149-57, 2009. (Pubmed) (DOI)

Jiang H, Reinhardt HC, Bartkova J, Tommiska J, Blomqvist C, Nevanlinna H, Bartek J, Yaffe MB, Hemann MT. The combined status of ATM and p53 link tumor development with therapeutic response. Genes Dev 23(16): 1895-909, 2009. (Pubmed) (DOI)

Mistrik M, Oplustilova L, Lukas J, Bartek J. Low-dose DNA damage and replication stress responses quantified by optimized automated single-cell image analysis. Cell Cycle 8(16): 2592-9, 2009. (Pubmed)

Blazkova H, Krejcikova K, Moudry P, Frisan T, Hodny Z, Bartek J. Bacterial Intoxication Evokes Cellular Senescence with Persistent DNA Damage and Cytokine Signaling. J Cell Mol Med. 2009 Jul 24. [Epub ahead of print] (Pubmed) (DOI)

Lindqvist A, de Bruijn M, Macurek L, Bras A, Mensinga A, Bruinsma W, Voets O, Kranenburg O, Medema RH. Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression. EMBO J 28(20): 3196-206, 2009. (Pubmed) (DOI)

Fugger K, Mistrik M, Danielsen JR, Dinant C, Falck J, Bartek J, Lukas J, Mailand N. Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities. J Cell Biol 186(5): 655-63, 2009. (Pubmed) (DOI)

Tanenbaum ME, Macurek L, Janssen A, Geers EF, Alvarez-Fernandez M, Medema RH. Kif15 cooperates with eg5 to promote bipolar spindle assembly. Curr Biol 19(20): 1703-11, 2009. (Pubmed) (DOI)

Novakova Z, Hubackova S, Kosar M, Janderova-Rossmeislova L, Dobrovolna J, Vasicova P, Vancurova M, Horejsi Z, Hozak P, Bartek J, Hodny Z. Cytokine expression and signaling in drug-induced cellular senescence. Oncogene 29(2): 273-84, 2010. (Pubmed) (DOI)

Bekker-Jensen S, Rendtlew Danielsen J, Fugger K, Gromova I, Nerstedt A, Bartek J, Lukas J, Mailand N. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol 12(1): 80-6; sup pp 1-12, 2010. (Pubmed) (DOI)

Macurek L, Lindqvist A, Voets O, Kool J, Vos HR, Medema RH. Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition. Oncogene. 2010 Jan 25. [Epub ahead of print] (Pubmed) (DOI)

Reviews

Zhou BB, Bartek J. Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Nat Rev Cancer 4(3): 216-25, 2004. (Pubmed) (DOI)

Lukas J, Bartek J. Watching the DNA repair ensemble dance. Cell 118(6): 666-8, 2004. (Pubmed) (DOI)

Bartek J, Lukas C, Lukas J. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 5(10): 792-804, 2004. (Pubmed) (DOI)

Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature 432(7015): 316-23, 2004. (Pubmed) (DOI)

Lukas J, Bartek J. Cell division: the heart of the cycle. Nature 432(7017): 564-7, 2004. (Pubmed) (DOI)

Bartek J, Lukas J. Cell biology. The stress of finding NEMO. Science 311(5764): 1110-1, 2006. (Pubmed) (DOI)

Bartek J, Mailand N. TOPping up ATR activity. Cell 124(5): 888-90, 2006. (Pubmed) (DOI)

Bartek J. Microcephalin guards against small brains, genetic instability, and cancer. Cancer Cell 10(2): 91-3, 2006. (Pubmed) (DOI)

Bartek J, Lukas J. Cell biology. Balancing life-or-death decisions. Science 314(5797): 261-2, 2006. (Pubmed) (DOI)

Oren M, Bartek J. The sunny side of p53. Cell 128(5): 826-8, 2007. (Pubmed) (DOI)

Groth A, Corpet A, Cook AJ, Roche D, Bartek J, Lukas J, Almouzni G. Regulation of replication fork progression through histone supply and demand. Science 318(5858): 1928-31, 2007. (Pubmed) (DOI)

Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science 319(5868): 1352-5, 2008. (Pubmed) (DOI)

Lukas J, Bartek J. DNA damage: a histone-code mediator leaves the stage. Nat Struct Mol Biol 15(5): 430-2, 2008. (Pubmed) (DOI)

Bartek J, Hodny Z, Lukas J. Cytokine loops driving senescence. Nat Cell Biol 10(8): 887-9, 2008. (Pubmed) (DOI)

Lukas J, Bartek J. DNA repair: New tales of an old tail. Nature 458(7238): 581-3, 2009. (Pubmed) (DOI)

Macurek L, Lindqvist A, Medema RH. Aurora-A and hBora join the game of Polo. Cancer Res 69(11): 4555-8, 2009. (Pubmed) (DOI)

Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature 461(7267): 1071-8, 2009. (Pubmed) (DOI)

Bartek J, Hodny Z. SUMO boosts the DNA damage response barrier against cancer. Cancer Cell 17(1): 9-11, 2010. (Pubmed) (DOI)