英国弗朗西斯克里克研究所Frank Uhlmann团队近期取得重要工作进展，他们研究发现了建立姐妹染色体凝聚力的复制叉决定因素。相关研究成果2023年1月23日在线发表于《细胞》杂志上。

据介绍，伴随着DNA复制，染色体黏连蛋白复合物在新复制的姐妹染色单体之间建立了凝聚力。凝聚力的建立需要通过Eco1乙酰转移酶将保守的内聚素赖氨酸残基进行乙酰化。

研究人员探讨了黏连蛋白乙酰化与DNA复制的联系。复制偶联黏连蛋白乙酰化的生化重建表明，在DNA复制过程中形成的瞬时DNA结构调控乙酰化反应。当聚合酶完成滞后链的复制时，链置换合成产生DNA垂悬物，这些DNA垂悬物被修剪以产生缺口的双链DNA。垂悬物和切口都能刺激黏连蛋白乙酰化，而随后的切口连接以完成冈崎片段成熟终止乙酰化反应。剥落或缺口的DNA构成了一条短暂的分子线索，将黏连白乙酰化引导到复制叉后面的一个窗口，黏连蛋白可能在这里捕获两个姐妹染色单体的位置。

总之，这一结果解释了DNA复制如何与姐妹染色单体的结合建立联系。

附：英文原文

Title: A replication fork determinant for the establishment of sister chromatid cohesion

Author: Masashi Minamino, Céline Bouchoux, Berta Canal, John F.X. Diffley, Frank Uhlmann

Issue&Volume: 2023-01-23

Abstract: 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.

DOI: 10.1016/j.cell.2022.12.044

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01587-2