Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Cohesion establishment requires acetylation of conserved cohesin lysine residues by Eco1 acetyltransferase. Here, we explore how cohesin acetylation is linked to DNA replication. Biochemical reconstitution of replication-coupled cohesin acetylation reveals that transient DNA structures, which form during DNA replication, control the acetylation reaction. As polymerases complete lagging strand replication, strand displacement synthesis produces DNA flaps that are trimmed to result in nicked double-stranded DNA. Both flaps and nicks stimulate cohesin acetylation, while subsequent nick ligation to complete Okazaki fragment maturation terminates the acetylation reaction. A flapped or nicked DNA substrate constitutes a transient molecular clue that directs cohesin acetylation to a window behind the replication fork, next to where cohesin likely entraps both sister chromatids. Our results provide an explanation for how DNA replication is linked to sister chromatid cohesion establishment.

伴随 DNA 复制，染色体黏附蛋白复合物在新复制的姐妹染色单体之间建立凝聚力。内聚力的建立需要通过 Eco1 乙酰转移酶对保守的内聚素赖氨酸残基进行乙酰化。在这里，我们探讨了 cohesin 乙酰化如何与 DNA 复制相关联。复制偶联黏连蛋白乙酰化的生化重建揭示了在 DNA 复制过程中形成的瞬时 DNA 结构控制着乙酰化反应。当聚合酶完成滞后链复制时，链置换合成产生 DNA 瓣，这些瓣被修剪以产生带切口的双链 DNA。皮瓣和缺口都刺激黏连蛋白乙酰化，而随后完成冈崎片段成熟的缺口连接终止了乙酰化反应。拍打或缺口的 DNA 底物构成了一个短暂的分子线索，它将粘连蛋白乙酰化作用引导到复制叉后面的窗口，紧挨着粘连蛋白可能捕获两个姐妹染色单体的地方。我们的结果解释了 DNA 复制如何与姐妹染色单体凝聚建立相关联。