In response to replication hindrances, DNA replication forks frequently stall and are remodelled into a four-way junction. In such a structure the annealed nascent strand is thought to resemble a DNA double-strand break and remodelled forks are vulnerable to nuclease attack by MRE11 and DNA2. Proteins that promote the recruitment, loading and stabilisation of RAD51 onto single-stranded DNA for homology search and strand exchange in homologous recombination (HR) repair and inter-strand cross-link repair also act to set up RAD51-mediated protection of nascent DNA at stalled replication forks. However, despite the similarities of these pathways, several lines of evidence indicate that fork protection is not simply analogous to the RAD51 loading step of HR. Protection of stalled forks not only requires separate functions of a number of recombination proteins, but also utilises nucleases important for the resection steps of HR in alternative ways. Here we discuss how fork protection arises and how its differences with HR give insights into the differing contexts of these two pathways.

为了应对复制障碍，DNA 复制叉经常停滞并被重塑为四向连接。在这种结构中，退火的新生链被认为类似于 DNA 双链断裂，并且重塑的叉很容易受到 MRE11 和 DNA2 的核酸酶攻击。促进 RAD51 招募、装载和稳定到单链 DNA 上以进行同源重组 (HR) 修复和链间交联修复中的同源搜索和链交换的蛋白质也可在以下位置建立 RAD51 介导的新生 DNA 保护：复制叉停滞。然而，尽管这些途径有相似之处，但一些证据表明分叉保护并不简单地类似于 HR 的 RAD51 加载步骤。保护停滞叉不仅需要许多重组蛋白的独立功能，而且还以其他方式利用对 HR 切除步骤很重要的核酸酶。在这里，我们讨论分叉保护是如何产生的，以及它与 HR 的差异如何让我们深入了解这两种路径的不同背景。