On September 3, 2025, our student and colleague Zuzana Machačová successfully defended her doctoral thesis entitled Molecular mechanisms regulating DNA replication, carried out under the supervision of Ing. Pavel Moudrý, Ph.D.
Her dissertation focused on the role of the DNA polymerase–primase complex (POLA) in the cellular response to poly(ADP-ribose) polymerase inhibitors (PARPi), a class of drugs widely used in cancer therapy. While PARPi are known to induce replication stress and DNA damage, the mechanism by which they accelerate replication fork progression has remained elusive. Zuzana’s work revealed that the POLA complex is a key factor driving replication fork acceleration upon PARPi treatment, and that depletion of its catalytic subunit POLA1 increases DNA gaps and enhances PARPi sensitivity—particularly in BRCA1-deficient cells. These findings not only provide new mechanistic insights into PARPi action but also propose POLA1 as a promising therapeutic target in BRCA1-deficient tumors.
A major part of her dissertation research resulted in a publication in Nature Communications, carried out in the Laboratory of Genome Integrity led by Mgr. Martin Mistrík, Ph.D.
Read the thesis HERE.
The Nature article is available HERE.
Congratulations!
Photo: Denisa Pavelková
