Departmental Seminar: Dr. Yosef Shiloh

Event Date: 1.6.2014 Day: Monday Time: 12:00 noon Location: 601 Fairchild (New Seminar Room on the 6th floor) Event Type: Departmental

Abstract

A central axis in maintaining genome stability is the DNA damage response (DDR) - a complex signaling network that is vigorously activated by critical DNA lesions such as double strand breaks (DSBs). The primary transducer of the DSB response is the serine-threonine kinase ATM. ATM is missing in patients with ataxia-telangiectasia (A-T), a prototype genomic instability syndrome. Following induction of DSBs, ATM mobilizes one of the most extensive signaling networks responding to specific stimuli, by directly or indirectly modifying a broad range of targets. Recent evidence suggests that ATM may play a role in the response to other types of genotoxic stress. Furthermore, ATM's broad capacity as a protein kinase may be exploited by undamaged cells for other signaling pathways, in response to various stimuli. We are exploring this network at the transcriptional and post-transcriptional levels using systems biology tools, and proteomic and genetic high-throughput screens. Subsequently, in-depth analysis of novel pathways is carried out. Important meeting points in this system being together players in the DDR and other arenas such as chromatin organization or the ubiquitin family. We are also examining the link between the DDR and aging, using cell biology methods and new animal models. The results indicate that sequence variations in genes that are involved in maintaining genomic stability, including ATM, may be affect morbidity and mortality in the general population including variations in aging pace among humans.