Final Report Summary - GLORI (Global analysis of R-loop structures (RNA-DNA hybrids) by advanced microscopic and genetic approaches)
Chromosomal breaks are usually associated with pathological disorders but a growing body of evidence point towards their role in a number of physiological processes, as meiotic recombination or class switch recombination. The main goal of this project was three-fold: first, we aimed to find associations between the occurrence of certain histone modifications / histone modifying enzymes, non-B DNA structures (e.g. RNA-DNA hybrids) and DNA damage formation (as DNA double-strand breaks (DSBs) and single-strand breaks (nicks). Second, we wished to understand how the molecular components of DNA breakage - associated or no with RNA-DNA hybrid formation - is embedded with higher-order chromatin architecture. Third, we wished to characterize protein factors that are involved in sensing, forming, stabilizing, and eliminating scheduled and unscheduled R-loop structures. Our investigations were performed in three model organisms, from S. cerevisiae to human cell lines, upon various metabolic settings and in mitotic and meiotic growth conditions.