Role for BLM in replication-fork restart and suppression of origin firing after replicative stress

Mutations in BLM give rise to Bloom's syndrome, a genetic disorder associated with cancer predisposition and chromosomal instability. Using a dual-labeling system in isolated chromosome fibers, we show that the BLM protein is required for two aspects of the cellular response to replicative stress: efficient replication-fork restart and suppression of new origin firing. These functions require the helicase activity of BLM and the Thr99 residue targeted by stress- activated kinases.