Chromatin loops protect replication forks during stress

Replication stress triggers the formation of protective chromatin loops around stalled replication forks. These loops enclose heterochromatin and are stabilized by CTCF, shielding forks from degradation. The formation of these loops requires CTCF anchoring and G9a-dependent heterochromatin deposition. Without this protective architecture, stalled forks become vulnerable to nucleolytic attack and degradation. This mechanism is crucial for genome integrity, particularly in cells with BRCA2 deficiency, where it safeguards replication initiation zones and prevents extensive DNA damage and mutations.