This R13 Conference grant proposal requests partial support for the 3rd US/EU Conference titled, 'Repair of Endogenous Genome Damage'. The broad objective of this Conference series is to promote discussion among scientists from US and EU countries about the recent advancements in processing of endogenous DNA damage (mostly oxidative) including repair and their role in cancer, other pathophysiologies and aging. An important objective of our meeting is exploration of collaborative efforts particularly among young investigators in two continents. The series was initiated with a meeting in Virginia in 2003 with great success. It was decided then that this conference series will continue to be held in alternate years and the venue will switch between a location in US and an EU country. Thus the 2nd conference was held in Sicily in November, 2005. For unavoidable reasons, the 3rd US/EU conference planned for 2007 was pushed back to November 5-9, 2008, and will be held in Moody Gardens Conference Center, Galveston, TX. The University of Texas Medical Branch in Galveston, the oldest medical school in Texas, will be a co-sponsor of this conference. The 4-day meeting will be attended by a little more than 100 participants including 45 invited speakers and session chairs, with equal representation from the US and EU. Special emphasis is placed on inclusion of young investigators both among invited speakers and poster presenters. Some of the posters will be selected for short oral presentation. Particular efforts will be made to include women and minority group scientists as speakers and other participants. The focus of this meeting is distinct from that of other, similar meetings because of its rather narrow focus on endogenous DNA damages. These damages are repaired primarily via the base excision and single- strand break repair (BER/SSBR) pathway. Multiple subpathways of BER/SSBR have evolved to process diverge damages. Furthermore, repair is regulated by multiple parameters, including tissue and cell types, cell cycle, cell differentiation, location of lesions in the genome and chromatin structures. New discoveries made in these areas and diseases due to repair deficiency identified since the meeting in 2005 will be discussed. Recent studies have suggested the existence of the BER interactome where the repair proteins interact with one another in a coordinated fashion. Age-dependent changes in repair of nuclear and mitochondrial genomes will also be covered. Comprehensive characterization of the repair processes should have significant translational implications. Finally, this conference devoted to discussion of the current state of our understanding, future directions and challenges by the leaders should be beneficial to the junior investigators in the repair field.
