The biogenesis of chromosome translocations

Repair of a chromosome break can result in part of a chromosome attaching to a different chromosome, causing gene deregulation and disease. Roukos and Misteli discuss the spatial aspect of chromosome translocation and the role of DNA repair pathways in this process. Chromosome translocations are catastrophic genomic events and often play key roles in tumorigenesis. Yet the biogenesis of chromosome translocations is remarkably poorly understood. Recent work has delineated several distinct mechanistic steps in the formation of translocations, and it has become apparent that non-random spatial genome organization, DNA repair pathways and chromatin features, including histone marks and the dynamic motion of broken chromatin, are critical for determining translocation frequency and partner selection.