EdU-seq profile in B,untreated and upon HU treatment

In this study, we map sites of replication initiation and breakage in primary cells at high resolution under conditions of replication stress. We show that replication initiates between transcribed genes within nucleosome-depleted structures established by long asymmetrical poly(dA:dT) tracts flanking the initiation site. Paradoxically, large (>20 bp) homopolymeric (dA/dT) tracts are also preferential sites of polar replication fork stalling and collapse. We propose that the evolutionary expansion of poly(dA:dT) tracts in eukaryotic genomes serves to promote replication initiation, but at the cost of increasing chromosome fragility. Overall design: EdU-seq profile in B,untreated and upon HU treatment.