Extended Data Figure 8: Stochastic loop tethering (activation) predicts apparent short-range negative interference.

a, In this model, DSBs A and B reside within a single loop domain (subject to tethering-dependent DSB formation), which is active in only a subpopulation of cells. The expected frequency of coincident DSB formation (double-cutting), assuming no DSB interference, is calculated for different frequencies of loop activation/tethering per chromatid assuming a model where DSB formation is wholly dependent on loop activation/tethering. In summary, loop activation/tethering at a frequency of X, will result in apparent negative interference of 1 – 1/X. See text for further details. b, c, Cartoons (left) and worked examples (right) for situations in which 50% (b) or 20% (c) of the chromatids within the assayed population are active/tethered at the test locus. The cartoons depict the tethering state of an average sample of 10 chromatids from the population. It is also possible that loop tethering and loop activation are not synonymous processes. In principle, activation of a loop might precede and enable tethering, but not be caused by it.