Local condensin defects and mitotic chromatin structure at CFSs. (A) Mechanistic model for cytological lesions. (i) Simulation setup investigating the consequences on chromatin structure of removing two condensin loops to model local depletion of condensins (the number of condensin bridges remains the same). (ii) Typical simulation snapshot. (iii) Images of mitotic chromosomes from RPE1 with DAPI staining after including replication stress with aphidocolin. Cytological lesions are visible (scale bar = 2.5 μm, see Materials and methods for additional information). (B) Mechanistic model for CFSs with irregular FISH phenotypes. (i) Simulation setup of another possible scenario associated with faulty condensin loading. In this case, three loops were joined together to create a single large loop (again condensin bridges remain the same): this scenario models faulty recruitment of condensin II, or in general of condensin looping activity. The violet segments mark the positions of the probes used in simulations to study how the FISH signal changes due to the perturbation shown. (ii) Typical simulation snapshot of the control case. (iii) Image of chromosomal defects visualized by FISH probes at a fragile site in control conditions in RPE1 cells (scale bar = 2.5 μm). (iv) Typical simulation snapshot for faulty condensin looping model. (v) Analogous FISH image at a CFS for RPE1 cells after depletion of the condensin component chromosome-associated protein H (CAP-H; scale bar = 2.5 μm). The simulated FISH probes appear to be close for the control case, while they separate when we model local faulty condensin looping, as in the experimental image.