Keywords: DNA repair, tumour, transcription Internship Duration: 01/01/22 - 30/06/22
Head of the hosting team: Tibor Pankotai Ph.D.
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Address of the host laboratory: Genome Integrity and DNA repair Team University of Szeged, Department of Pathology, Pankotai laboratory Állomás u. 1. 6725 Szeged Hungary
Supervisor: Tibor Pankotai Ph.D.E-mail: pankotai.tibor@szte.hu Phone: +3662546164
Faithful repair of DNA double-strand breaks (DSBs) is indispensable, since improper repair can lead to genome instability, then tumorigenesis. DSBs can be repaired through different pathways, and the balance between the choice of them must be tightly regulated to preserve genome integrity. DNA damage can be considered as a harmful stressor which various biochemical pathways are activated, ensuring the proper DNA repair and cell survival. The main focus of the project is to map the signalling circuit induced by DNA damage, including the steps of cell-cell communication mechanism, which is initiated by the damaged cell. In our experimental setup, we will use state-of-the-art biochemical technologies in a human cell culture model system, and we will validate the data obtained at single-cell level by using super-resolution STORM microscopy. With our experiments, we can verify the existence and the means of exosome-mediated cellular communication induced by DNA damage processes. Furthermore, our goal is to reveal how small RNAs are transcribed from the damaged genomic locus by de novo transcription which are involved in exosomal cell-cell communication. As a result of the project, we can understand the cellular response processes induced by DNA repair mechanism by exploring the key steps in this process that might help the undamaged cells prepare for faster repair in case of a potential DNA damage.
Our laboratory focuses on understanding the process of cancer formation and how genome integrity and maintenance changes during this processes. We use genetic, biochemical, functional genomic and proteomic approaches in mammalian cells. We use innovative in vitro and in vivo methodswhich involves wide-range of knowledge in the field of DNA repair, transcription and tumour biology. The techniques used in the lab covers the methodology used in early tumour marker detection, chromatin immunoprecipitation, STORM microscopy and NGS approaches as well as maintaining cell culture and .
1. Quantification of DNA damage induced repair focus formation via super-resolution dSTORM localization microscopy. Varga D , Majoros H , Ujfaludi Z , Erdélyi M , Pankotai T . Nanoscale. 2019 Aug 1;11(30):14226-14236. doi: 10.1039/c9nr03696b. 2. WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks. Caron P, Pankotai T, Wiegant WW, Tollenaere MAX, Furst A, Bonhomme C, Helfricht A, de Groot A, Pastink A, Vertegaal ACO, Luijsterburg MS, Soutoglou E, van Attikum H.
