Nascent RNA profile in B, and T cells 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. Nascent RNA profile in B, and T cells untreated and upon HU treatment.

本研究在复制应激条件下，以高分辨率绘制了原代细胞内复制起始与断裂位点的图谱。研究表明，复制起始发生于转录基因之间的核小体缺失结构（nucleosome-depleted structure）内，该结构由起始位点侧翼的长不对称聚(dA:dT)序列（poly(dA:dT) tracts）所构建。矛盾的是，长度大于20碱基对（bp）的同聚物(dA/dT)序列同时也是极性复制叉停滞与崩解的偏好性位点。我们提出，真核基因组中聚(dA:dT)序列的进化扩张旨在促进复制起始，但却以增加染色体脆性为代价。本数据集同时包含未经处理及经HU处理的B细胞与T细胞的新生RNA谱。