3D Genome Organization Influences the Chromosome Translocation Pattern.

Recent imaging, molecular, and computational modeling studies have greatly enhanced our knowledge of how eukaryotic chromosomes are folded in the nuclear space. This work has begun to reveal how 3D genome structure contributes to various DNA-mediated metabolic activities such as replication, transcription, recombination, and repair. Failure of proper DNA repair can lead to the chromosomal translocations observed in human cancers and other diseases. Questions about the role of 3D genome structure in translocation mechanisms have interested scientists for decades. Recent applications of imaging and Chromosome Conformation Capture approaches have clarified the influence of proximal positioning of chromosomal domains and gene loci on the formation of chromosomal translocations. These approaches have revealed the importance of 3D genome structure not only in translocation partner selection, but also in repair efficiency, likelihood of DNA damage, and the biological implications of translocations. This chapter focuses on our current understanding of the role of 3D genome structure in chromosome translocation formation and its potential implications in disease outcome.