TRIP · A TRIP through chromatin and DNA double strand break repair

Genes tend to aggregate, nucleotide usage tends to change over large domains and yet, reasons for this are poorly understood. This suggests that there exists unknown molecular processes at work for millions of years and that shape the structure of modern genomes. Understanding the organization of genomes is another way to look into these molecular processes. Particularly relevant are DNA repair and chromatin processes, which can have a significant impact on the global organization of a genome. In this project, we hammer out the concept of chromatin print; which represents the effect of the local chromatin structure on the evolution of genomes through DNA repair. The existence of the chromatin print is no longer to be established, but the nature and strength of the phenomenon escape experimentation for lack of appropriate technologies. We are developing a method called TRIP for Thousands of Reporters In Parallel to precisely tackle this issue. The goal of this project is to develop and use TRIP to obtain a genome-wide dataset revealing how double-strand breaks occur and are repaired in different chromatin environments. This will give a clearer picture of the evolution of regulatory sequences and of the strength of the chromatin print. In the long term, knowledge of mutation-prone sequences might be used for routine prenatal checks of human syndromes caused by de novo mutations such as autism.