Dealing with dangerous accidents: DNA double-strand breaks take centre stage. Symposium on Genome Instability and DNA Repair

The Keystone Symposium on Genome Instability and DNA Repair took place between 1 and 6 March 2009, in Taos, New Mexico, and was organized by M. Jasin, S.J. Elledge & M.S. Neuberger. ![][1] See Glossary for abbreviations used in this article DSBs occur when both strands of a DNA double helix are damaged by either the normal metabolic processes of the cell, or environmental factors such as ultraviolet light or radiation. Cells have evolved mechanisms to repair DSBs, to ensure that large pieces of the genome are not lost; however, the aberrant repair of DSBs can lead to genome rearrangements that scramble the information encoded in the DNA. The 2009 Keystone Symposium on Genome Instability and DNA Repair featured mechanistic studies of DSB repair, host responses to DSBs and recent phenomenology in human genomic disorders. This report highlights some of the key findings presented at the meeting. Space limitations have prevented us from discussing every contribution, and we apologize to those whose work is not highlighted in this report. One way to understand the consequences of aberrant DSB repair is to identify and characterize genomic rearrangements. M. Stratton (Cambridge, UK) used second‐generation whole‐genome DNA‐sequencing technologies to characterize the most common types of DNA rearrangement in a range of cancer cell lines and primary tumours. In addition to finding a large number of point mutations in these samples, preliminary analyses of the data indicate that many rearrangements result from intrachromosomal events, and, less frequently, interchromosomal breakage and rejoining events. Importantly, many of these rearrangements had not been seen previously because they are too small to be detected by conventional karyotype analyses. The analysis of junction sequences by the Stratton group also revealed that classical repair processes such as HR and NHEJ, probably have a role in the formation of these rearrangements. However, … [1]: /embed/graphic-1.gif