Drosophila as a new tool to study the chromatin structural changes activated by DNA damages

Szűcs, Diána and Varga, Árpád and Viszinger, Evelin and Berzsenyi, Ivett and Ollé, Bence and Borsos, Barbara and Páhi, Zoltán Gábor and Majoros, Hajnalka and Újfaludi, Zsuzsanna and Pankotai, Tibor (2016) Drosophila as a new tool to study the chromatin structural changes activated by DNA damages. In: Annual Meeting of the Hungarian Biochemical Society, 2016, Szeged.

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Abstract

In eukaryotic cells, any processes which involve DNA have to take place in the context of chromatin structure, which affects the probability of the dam-aging agents to cause DNA breaks and the recruit-ment of the repair proteins. The improper repair or persistence of breaks leads to genome instability, which could result in tumor formation. Our goal is to understand what makes cells able to recognize the appearance of DNA break and how the chromatin structure could change around the break. The an-swers to these questions will provide information on whether specific chromatin structures predispose sites for DNA break and whether memory of previ-ous break is retained in the chromatin structure. We started to setup human cell culture-based and Drosophila experimental systems by which we could study how unique histone post-translation-al modifications (PTMs) could affect the DNA repair. We take advantage of the model system where we delete the endogenous histone cluster and we substitute it with mutant histones which permits or mimics unique histone PTMs. We have already started to mutate histone genes and screen 50 different histone PTMs. We will use these flies to check the DNA repair kinetics in those animals which consist of only the mutated histones. Using the Drosophila and the human cell culture based system we have already identified new H3 and H4 histone PTM candidates that play role in chromo-somal rearrangement which could influence the DNA repair processes. The system developed in our laboratory would help in understanding the mecha-nisms, which give rise to frequent chromosomal break points often detected in tumors. Progress in integrating the chromatin dimension in DNA repair will help to understand how DNA damage may impact on genome stability. These results would also help identifying new key targets in DNA dam-age repair and the final goal of the project is to find potential biomarkers which could be used in anti-cancer therapies. Supported by OTKA-PD [112118] and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

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