Centromeres are stress-induced fragile sites

This thesis discusses the concept of centromeres as stress-induced fragile sites, emphasizing their susceptibility to unwinding under mechanical tension. Tension can arise from microtubule pulling forces during cell division or from changes in supercoiling energy. This work presents evidence of centromere DNA that can unwind thus providing substrates amenable to recombination via a DSB. The unwinding and recombination occur in the context of increased stress, either constitutive or induced.The research presented highlights a novel mechanism for recombination at centromeres, suggesting that they can act as local tension relief valves. According to the proposed model, when subjected to high tension, yeast centromeres experience frequent breakage thus alleviating stress and, via subsequent repair, restoring proper balance of tension. Our findings are significant as they provide insights into how centromeres maintain their integrity and functionality during the dynamic processes of cell division. Additionally, this work connects observations to recent advancements in mapping mammalian sequences, where prominently expanding satellite sequences have been identified at centromeres, particularly in regions experiencing high force production.Overall, this work contributes to a deeper understanding of centromere biology, particularly in the context of mechanical stress and its implications for genomic stability and evolution. The findings underscore the importance of centromeres not only as structural components of chromosomes but also as dynamic entities that can respond to physical forces in the cellular environment.