Duplication of mammalian genomes requires replisomes to overcome numerous impediments during passage through open (eu) and condensed (hetero) chromatin. Typically, studies of replication stress characterize mixed populations of challenged and unchallenged replication forks, averaged across S phase, and model a single species of “stressed” replisome. Here, in cells containing potent obstacles to replication, we find two different lesion proximal replisomes. One is bound by the DONSON protein and is more frequent in early S phase, in regions marked by euchromatin. The other interacts with the FANCM DNA translocase, is more prominent in late S phase, and favors heterochromatin. The two forms can also be detected in unstressed cells. ChIP-seq of DNA associated with DONSON or FANCM confirms the bias of the former towards regions that replicate early and the skew of the latter towards regions that replicate late.

哺乳动物基因组的复制需要复制体来克服通过开放 (eu) 和凝聚 (hetero) 染色质过程中的众多障碍。通常，复制应激研究表征受攻击和未受攻击复制叉的混合种群，在 S 期平均，并对单一物种的“受压”复制体进行建模。在这里，在含有强大复制障碍的细胞中，我们发现了两种不同的病变近端复制体。一种与 DONSON 蛋白结合，在早期 S 期、常染色质标记区域中更常见。另一个与 FANCM DNA 转位酶相互作用，在 S 期后期更为突出，有利于异染色质。这两种形式也可以在未受压的细胞中检测到。