GENOME INTEGRITY

doc. Mgr. Lumír Krejčí, Ph.D.

E-mail: lumir.krejci@fnusa.cz

Key words

Genome Integrity, DNA Repair, Homologous Recombination, Cancer, Small Molecule Inhibitors.

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.

Main goals

  • 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.

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.