单体 ZRANB3 驱动复制叉逆转
Monomeric ZRANB3 drives replication fork reversal
单体 ZRANB3 在复制叉连接处结合 DNA，是催化复制叉逆转的最小功能单元。研究结合生化、生物物理与单分子方法，发现 ZRANB3 以 ATP 依赖的局部双链解开配合 ATP 非依赖的链退火促成四向连接形成，再经定向分支迁移实现长距离复制叉逆转；单分子荧光实验证实单体 ZRANB3 足以驱动该过程。
来源：Nucleic Acids Research · doi.org
Replication fork reversal is a central response to replication stress, yet how a SNF2 translocase coordinates the distinct mechanical steps required for this reaction remains elusive. Here, we define the mechanism by which ZRANB3 catalyzes fork reversal using biochemical, biophysical, and single-molecule approaches. ZRANB3 binds fork DNA as a monomer at the junction, establishing the minimal functional unit required for activity. Mechanistically, ZRANB3 combines ATP-dependent localized duplex opening with ATP-independent strand annealing to facilitate four-way junction formation, followed by directional branch migration that supports long-range fork reversal. Single-molecule fluorescence analyses further demonstrate that monomeric ZRANB3 is sufficient to drive fork reversal. Together, these findings define how ZRANB3 integrates distinct DNA remodeling activities within a single enzyme to catalyze fork reversal.