Speaker: Prof. Giovanni Capranico
University of Bologna – Dept. of Pharmacy and Biotechnology
Title:
Genome context affects the mechanistic response to non-B DNA structure imbalance.
Abstract:
Transcription/replication conflicts (TRC) are frequent in highly transcriptionally active cancer cells favouring cancer progression and resistance to therapy. Camptothecin can poison DNA topoisomerase I (Top1) by delaying strand-rejoining enzyme activity, thus increasing substantially the half-life of the so-called Top1cc (Top1-DNA cleavage complex). Top1ccs can rapidly lead to DNA cleavage, TRCs and genome instability. At the same time, excessive G-quadruplex structures can also increase gene instability by impairing DNA replication process. The mechanisms of genome instability due to replication stress caused by Top1 poisoning or stabilized G-quadruplexes are genome-context dependent. Recently, we have investigated how Top1ccs can impair transcription elongation by looking at RNAPII pausing/backtracking. The new data show that Top1ccs effectively induce pausing and backtracking of RNAPII genome wide. In addition, Top1 depletion can cause elongation impairment by at different genomic sites. Bioinformatic and chromatin visualization technologies have allowed us to accumulate data supporting that co-directional TRCs are frequently caused by Top1ccs preferentially at 5’ ends of active genes in early replicating zones, defining a previously-unrecognized mechanism of Top1cc-induced TRCs and genome instability.
Biosketch
Giovanni Capranico is a Full professor of Molecular biology at the University of Bologna, and Group leader at IRCCS-Sant’Orsola Hospital in Bologna, Italy. He spent two years at NIH, Bethesda, USA and worked as Principal Investigator at the National Cancer Institute in Milan. He became full professor in 2006 at Bologna University. His research focuses on cancer genome instability and the interplay with immunomodulation. He has an h-index = 61 (Google Scholar) and has mainly been funded by Associazione Italiana per la Ricerca sul Cancro (AIRC), Italian Ministry of Research and University, French-Italian University Vinci and industries. He has two patents