Group leader: Gyula Timinszky

Email: timinszky.gyula[at]brc.hu

Group website:

Group members

Name

Title

 

 

Gyula TIMINSZKY

Senior research associate

publications

CV

László HENN

Research associate

publications

CV

Roberta FAJKA-BOJA

Senior research associate

 

 

Ágnes Czibula

Senior research associate

 

 

Hasan MAMAR

Junior research associate

 

CV

Mihály MÉREY

PhD student

 

CV

Alexandra MIHUT

PhD student

 

CV

Mohd Saifullah ANSARI

PhD student

 

 

Anna Georgina KOPASZ

PhD student

 

CV

Adrián KÓSZÓ

Laboratory assistant

 

 

Research                                           

Genome integrity is crucial for all living organisms. If damaged DNA is not promptly repaired, the mutations ultimately lead to the development of cancer. Defective repair can also cause immunodeficiency, neurodegenerative disorders and premature ageing. The range of DNA lesions require diverse signaling and repair pathways to shape the DNA damage response. This involves changes in nuclear dynamics including alterations in chromatin structure, nucleocytoplasmic transport and protein activities.

ADP-ribosylation is one of the earliest post-translational modifications appearing upon DNA damage. Its effects are numerous. One of its functions is to relax chromatin at the sites of DNA damage, facilitating the access of DNA repair processes to the lesions. Our findings indicate that nuclear dynamics, mRNA metabolism and chromosome organization strongly depend on nuclear ADP-ribosylation reactions and their crosstalk with other signaling pathways. Its deregulation impairs DNA repair and is implicated in cancer. At the bedside, the inhibition of ADP-ribosylation by drugs is used to treat cancer with certain gene mutations.

Our research goal is to characterize novel molecular mechanisms that regulate the DNA damage response, including nucleocytoplasmic transport, mRNA metabolism and chromatin architecture. We study novel cancer relevant mutations that are sensitive to ADP-ribosylation inhibitors, which could be potentially used to treat tumors carrying such mutations. Furthermore, we investigate the molecular basis of a DNA damage-induced nuclear export mechanism that regulates ADP-ribose metabolism.