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Čeština

Genome Integrity

Our team investigates fundamental mechanisms and translates findings from bench to bedside, combining preclinical models with clinical insight.

Researcher at ICRC with focus on translational medicine. Combines preclinical insights with clinical practice across cardiology, neurology, and oncology programs.

Currently leads / contributes to interdisciplinary projects bridging molecular biology, imaging, and patient care at St. Anne's University Hospital Brno.

Research Group

Team size
Team size: 2 Researchers
Place
Place: Building B1, 4th Floor
Collaborates with
Collaborates with Czech Academy of Sciences

Head of Research Group

doc. Mgr. Lumír Krejčí, Ph.D.
lumir.krejci@fnusa.cz
doc. Mgr. Lumír Krejčí, Ph.D.
doc. Mgr. Lumír Krejčí, Ph.D.

Team Assistant

Main Objectives

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

Research focus

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.

The detail study of nucleases, which comprise an integral part of many DNA repair pathways and their inactivation, leads to genomic instability and cancer.

Various methods from biochemistry, structural biology, molecular biology, genetics and biophysics.

Detail study of protein properties and activities including their interaction with other molecules such as DNA, smallmolecule inhibitors.

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.

Selected Results

  • Spirek M, Taylor MRG, Belan O, Boulton SJ, Krejci L*. Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function. Nat. Commun. 2021, 5554. https://doi.org/10.1038/s41467-021-25830-x.
  • Feretzaki, M., Pospisilova, M., Valador Fernandes, R., Lunardi T., Krejci, L*, Lingner J. RAD51- dependent recruitment of TERRA lncRNA to telomeres through R-loops. Nature (2020). https://doi.org/10.1038/s41586-020-2815-6
  • 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. Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments. Mol. Cell. 2017 67(5), 867658-+. DOI: 10.1016/j.molcel.2017.07.001
  • Di Marco S, Hasanova Z, Kanagaraj R, Chappidi 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. RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Mol. Cell. 2017, 66(5), 658-+. DOI: 10.1016/j.molcel.2017.05.006
  • Taylor MR, Špírek M, Jian Ma C, Carzaniga R, Takaki T, Collinson LM, Greene EC, Krejci L*, Boulton SJ. A Polar and Nucleotide-Dependent Mechanism of Action for RAD51 Paralogs in RAD51 Filament. Mol. Cell. 2016, 64(5), 926-939. DOI: 10.1016/j.molcel.2016.10.020
  • Taylor MRG, Spirek M, Carasiya KR, Ward JD, Carzaniga R, Yu X, Egelman EH, Collinson LM, Rueda D, Krejci L*, Boulton SJ. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. Cell 2015, 162(2), 271-286. DOI: 10.1016/j.cell.2015.06.015
  • Krejci L*, Van Komen S, Li Y, Villemain J, Reddy MS, Klein H, Ellenberger T, Sung P. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature 2003, 423, 305-9. DOI: 10.1038/nature01577
Genome Integrity Genome Integrity Genome Integrity