Research focus

The Genome Integrity research focuses on deciphering the intrinsic functions of homologous recombination (HR) which has a dual role in the maintenance of genome stability. First, it promotes the faithful repair of DNA double-strand breaks belonging among of the most lethal forms of DNA damage. Moreover, HR is required also for stabilizing stalled replication forks, promoting their reversal, protection and restart to ensure completion of replication and ensure genome maintenance. Inability to perform and regulate recombination is linked to human infertility, miscarriage and genetic diseases, particularly cancer further emphasizing the importance of better mechanistic understanding of this pathway. Furthermore, the GENI group focuses on the detail study of nucleases which comprise an integral part of many DNA repair pathways and their inactivation leads to genomic instability and cancer.

Research objectives

  • Characterization the mechanismand regulation of homologous recombination and its intrinsic role in the maintenance of genome stability.
  • Mechanistic understanding of the action of HR co-factors and their impact on genome integrity and cancerogenesis.
  • Development of potent and selective inhibitors of nucleases for possible therapeutic use.

Main partners

  1. Francis Crick Institute, London, UK
  2. University of Zurich, Zurich, Switzerland
  3. IFOM, Milan, Italy

Technological equipment

  • Atomic Force Microscopy-a powerful microscopy technology for studying samples at nanoscale providing an image in three-dimensional topography as well as various types of surface measurements.
  • DeltaVision Elite Microscopy System - a fully integrated high-resolution, fluorescence microscopy platform optimized for low-light imaging of live cells and general fluorescence imaging applications.

Offered services and expertise

  • Various methods from biochemistry, structural biology, molecular biology, genetics and biophysics.
  • Detail study ofprotein properties and activities including their interaction with other molecules such as DNA, smallmolecule inhibitors.

Top publications

  • KOLINJIVADI, AM, SANNINO, V, DE ANTONI, A, Zadorozhny, K, Kilkenny, M, Techer, H, Baldi, G, Shen, R, Ciccia, A, Pellegrini, L, Krejci, L*, Costanzo, V. (2017) Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments. Mol Cell. 67 (5): 867658.
  • DI MARCO, S, HASANOVA, Z, KANAGARAJ, R, CH, N, ALTMANNOVA, V, MENON, S, SEDLACKOVA, H, LANGHOFF, J, SURENDRANATH, K, HUHN, D, BHOWMICK, R, MARINI, V, FERRARI, S, HICKSON, ID, KREJCI, L*, JANSCAK, P. (2017) RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Mol Cell. 66 (5): 658-+. DOI: 10.1016/j.molcel.2017.05.006. IF= 14.248
  • TAYLOR MR, ŠPÍREK M, JIAN MA C, CARZANIGA R, TAKAKI T, COLLINSON LM, GREENE EC, KREJCI L*, BOULTON SJ.  (2016) A Polar and Nucleotide-Dependent Mechanism of Action for RAD51 Paralogs in RAD51 Filament. Mol Cell. 64 (5): 926-939
  • TAYLOR, M., ŠPÍREK, M., CHAURASIYA, K., WARD, J., CARZANIGA, R., YU, X., EGELMAN, E., COLLINSON, L., RUEDA, D., KREJČÍ, L., BOULTON, S. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. Cell. 2015, 162(2), 271-286.
  • KREJCI, L.*, VAN KOMEN, S., LI, Y., VILLEMAIN, J., REDDY, M. S., KLEIN, H., ELLENBERGER, T., SUNG, P. (2003) DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 423:305-9.

Other selected results

  • Several studies deciphering the essential role of post-translational modification SUMOylationand its effect on the function of various HR proteins.
  • Discovery of the mechanism how Rad51 paralogs stimulates the function of Rad51 during HR.

Team members

  • doc. Mgr. Lumír Krejčí, Ph.D.
  • Mgr. Gabriela Pavlíková
  • Masaki Akita
  • Atis Jekabsons, MSc
  • Mgr. Kateřina Krejčí, Ph.D.
  • Mgr. Maria Victoria Marini Palomeque, Ph.D.
  • Mgr. Jarmila Mlčoušková, Ph.D.
  • Fedor Nikulenkov, Ph.D.
  • RNDr. Jana Procházková, Ph.D.
  • Ing. Monika Siekelová
  • RNDr. Mário Špírek, Ph.D.
  • Bc. Magdaléna Zacpalová

Principal Investigator

doc. Mgr. Lumír Krejčí, Ph.D.
doc. Mgr. Lumír Krejčí, Ph.D.
Principal Investigator

Assistant

Mgr. Gabriela Pavlíková
Mgr. Gabriela Pavlíková
Koordinátor projektu