Recombination Mechanisms and
Genome Instability

DNA is a highly reactive molecule that is susceptible to damage. Fortunately, cells have evolved specialized repair processes that are remarkably efficient in correcting specific types of DNA damage. Failure to correctly repair DNA damage is associated with genome instability and mutagenic change, which accelerates ageing and the onset of cancer. The most cytotoxic DNA lesion is the DNA double-stranded DNA break (DSB), which can arise following exposure to genotoxic agents and following the collapse of stalled replication forks. In eukaryotic cells, DSBs can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). Given the frequency of genome breakage during replication, HR plays a key role during DNA replication to ensure genome integrity and faithful transmission of genetic information during cell division. HR is also essential for meiotic DSB repair and the production of gametes for sexual reproduction. The importance of HR to human health is highlighted by the fact that mutations in HR genes are causal for a number of cancer predisposition syndromes (eg. hereditary breast and ovarian cancer is caused by mutations in the HR genes BRCA1 or BRCA2). Our understanding of the mechanism of HR repair and its importance for the maintenance of genome integrity has been advanced by significant developments in a number of areas. Biochemical, structural studies and single molecular approaches have led to an improved understanding of the mechanism of key recombination proteins. Recent advances in imaging techniques have accelerated our understanding of how recombination proteins relocate to sites of DNA damage. Of particular interest is the realization that HR and DSB repair proteins are intimately linked to other nuclear processes, including transcription, RNA export or RNA processing. The field is also beginning to understand how the cell cycle machinery and chromatin context influences the choice of DSB repair pathway. The principal aim of the meeting will be to discuss the new advances in our understanding of the factors and mechanims responsible for homologous recombination both in mitosis and meiosis from model organisms to human cells, as well as the interplay between recombinational repair and other cellular processes, including DNA replication, chromosome dynamics, chromatin structure, cell cycle, DNA damage response, RNA-mediated nuclear events and nuclear structure.

The main aim of the meeting is to discuss new and unpublished results. A good number of short talks will be reserved for participants. Extensive time and opportunities for discussions on new data will be a primary goal for the meeting.

Topics will include:

• Genetics and Biochemistry of recombination
• Replication-recombination interface
• Recombination mechanisms
• Meiotic recombination
• DNA damage response
• Chromosome structure and cohesion
• Genome rearrangements
• Interplay between DSB repair and other nuclear processes
• DSB repair and human disease