Replication-stress loops shield forks with CTCF and G9a-driven heterochromatin
Under replication stress, cells form transient chromatin loops that enclose de novo, heterochromatin-enriched stalled forks. These loops are anchored by ATR-dependent CTCF and stabilized by G9a-mediated H3K9me3, creating a protective scaffold that limits nuclease access and preserves fork integrity; disrupting the loop framework increases nascent-DNA degradation, a vulnerability that extends to BRCA2-deficient cells, highlighting 3D genome reorganization as a key mechanism to mitigate mutagenesis during replication stress.