Fig. 1: EdU-seq in S, G2, and M phases reveals the dynamics of fragile site replication.

Panels show idealized signal peaks seen at the largest human genes associated with CFSs when EdU-seq is restricted to different cell cycle stages. a Transcription enforces extremely large replicons by suppressing internal origin firing, such that MiDAS (red color) is required to rescue replication in M phase when fork progression is impeded (even large genes usually complete replication in S phase without replication stress; gray color). b In cell types with less effective DNA damage responses, more rapid progression to M phase leads to the appearance of “twin peaks” of MiDAS signal that highlight the long distances traveled by the non-canonical low-fidelity forks associated with BIR.