Group Leader: Tibor Pankotai Ph.D., habil
Nuclear dynamics of DNA repair, as a potential target for improved early detection and risk control of tumorigenesis (aDDRess project)
Tumour development may be regarded as an epigenetic- and transcription-coupled malfunction. Tumour transformation of a normal cell is triggered and regulated by alteration of the tissue-specific epigenetic landscape followed by transcriptional reprogramming in which the expression of genes responsible for maintaining the differentiation potency of stem cells becomes upregulated, leading to an unsupervised dedifferentiation. On the other side, in eukaryotic cells, the chromatin structure can influence DNA repair processes by affecting the accessibility of DNA repair factors to the damaged site. The aim of the aDDRess project is to characterize the role of chromatin regulators and histone modifications during the DDR and reveal the mechanism how these changes can initiate the tumour development. To understand the mechanistic role of this process, we apply Chromatin Immunoprecipitations combined with NGS to demonstrate the co-localization of repair proteins with known histone modifications involved in DDR. These genome-wide data is validated by single-cell super-resolution STORM microscopy to aDDRess their dynamics and impacts on the assembly of DNA repair machinery at the break site. As an extension of the project, we aDDRess and characterize chromatin markers, which can have predictive values in human clinical diagnostics. According to this histone post-translational modifications can be potential candidates in tumour diagnostics in cells lacking functional DNA repair pathways. Therefore, it can contribute to the detection and qualification of tumours even in the early stage of cancer development.