Institute of Animal Pathology

Genome Dynamics

We investigate various aspects of genome dynamics that integrate ADP-ribose metabolism and RNA biology in the context of genome maintenance and expression in normal and pathological situations, including cancer and neurological diseases, especially neurodegeneration. We explore the molecular mechanisms by which DNA strand breaks are detected and repaired and we are particularly interested in identification and characterization of protein factors and pathways that link aberrant ADP-ribose and/or RNA metabolism to neurodegenerative disease. We aim to examine whether the deregulated ADP-ribose metabolism at sites of DNA breaks extends beyond rare DNA repair-defective diseases to dementia, a neurodegenerative disease that presents the greatest threat to normal ageing and health. The cause of neurodegenerative disorders is often genetic; however, the involved genes and the underlying mechanisms are increasingly diverse, indicating the complexity of brain development and growth. Additionally, since several infections have been associated with the risk of cognitive impairment and neurodegeneration, we investigate the effect of bacteria- and virus-derived stimuli on the disease onset and progression. Ultimately, we envisage that our work will lead to new therapeutic avenues for the clinical treatment of neurodegenerative disease.

Cerebellum

Team

Group leader

Staff

The rest of the team is based in the Hanzlikova’s group at the IMG in Prague

Publications

key publications

  • Hrychova, K., K. Burdova, Z. Polackova, D. Giamaki, B. Valtorta, J. Brazina, K. Krejcikova, B. Kuttichova, K. W. Caldecott and H. Hanzlikova (2024). "Dispensability of HPF1 for cellular removal of DNA single-strand breaks." Nucleic Acids Res 52(18):10986-10998. [doi]
  • Cihlarova, Z., J. Kubovciak, M. Sobol, K. Krejcikova, J. Sachova, M. Kolar, D. Stanek, C. Barinka, G. Yoon, K. W. Caldecott and H. Hanzlikova (2022). "BRAT1 links Integrator and defective RNA processing with neurodegeneration." Nat Commun 13(1): 5026. [doi]
  • Vaitsiankova, A., K. Burdova, M. Sobol, A. Gautam, O. Benada, H. Hanzlikova* and K. W. Caldecott* (2022). "PARP inhibition impedes the maturation of nascent DNA strands during DNA replication." Nat Struct Mol Biol 29(4): 329-338. [doi] *corresponding author
  • Hanzlikova, H.*, E. Prokhorova, K. Krejcikova, Z. Cihlarova, I. Kalasova, J. Kubovciak, J. Sachova, R. Hailstone, J. Brazina, S. Ghosh, S. Cirak, J. G. Gleeson, I. Ahel and K. W. Caldecott* (2020). "Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair." Nat Commun 11(1): 3391. [doi] *corresponding author
  • Hanzlikova, H.*, I. Kalasova, A. A. Demin, L. E. Pennicott, Z. Cihlarova and K. W. Caldecott* (2018). "The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication." Mol Cell 71(2): 319-331 e313. [doi]  *corresponding author
  • Hanzlikova H. & N. C. Hoch, S. L. Rulten, M. Tetreault, E. Komulainen, L. Ju, P. Hornyak, Z. Zeng, W. Gittens, S. A. Rey, K. Staras, G. M. Mancini, P. J. McKinnon, Z. Q. Wang, J. D. Wagner, C. Care4Rare Canada, G. Yoon and K. W. Caldecott (2017). "XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia." Nature 541(7635): 87-91. [doi]

For a complete overview of the publications please see at ORCiD

Open positions

Outstanding young scientists interested in PhD or postdoctoral positions in the Hanzlikova lab should contact Hana directly at hana.hanzlikova@unibe.ch.