Anchoring Chromatin Loops to Cancer

Abstract

Although some genomic rearrangements are caused by replication or transcription, the etiology of others is unclear. Reporting in Cell, Canela et al. (2017) reveal that type II topoisomerase-mediated release of torsional strain at chromosomal loop anchors generates DNA double-strand breaks that drive multiple oncogenic translocations in a transcription-independent manner.

Figure 1. Model for How DNA Damage Occurs at Chromatin Loop Anchors

After recruitment by the cohesin loader, cohesin slides along chromatin, extruding a chromatin loop and inducing torsional strain in the chromosome, until its movement is stopped by encountering CTCF. Topoisomerase TOP2B is recruited to the chromatin loop anchor to relieve the torsional strain by breaking and resealing the DNA, but occasionally it does not reseal the breaks, leading to oncogenic chromosome rearrangements.