Scholarlink

<p>Replication fork reversal helps maintain genomic stability during replication stress. F-box helicase 1 (FBH1) catalyzes fork reversal and is an SCF (SKP-CUL1-F-box) E3 ubiquitin ligase that limits RAD51 association with chromatin. Here, we show that preferential binding of SCF<sup>FBH1</sup> to the lagging strand template at DNA fork structures stimulates helicase activity and is required for fork reversal. A cryo-EM structure of SCF<sup>FBH1</sup> bound to DNA representing a stalled fork reveals an intimate interaction between FBH1 and the fork junction. Disruption of this interface severely curtails fork reversal in vitro and replication progression in cells, providing a model for how ssDNA translocation by FBH1 facilitates annealing of parental DNA by a fundamentally different mechanism than the fork remodelers SMARCAL, HLTF, and ZRANB3. The structure provides a model for SCF<sup>FBH1</sup> disassembly of RAD51 filaments through translocation and ubiquitination, and implies that RAD51 is associated with the lagging strand at stalled forks.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structural basis for fork reversal and RAD51 regulation by the SCF ubiquitin ligase complex of F-box helicase 1

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月26日

查看全文
  • Briana H. Greer,
  • Javier Mendia-Garcia,
  • Elwood A. Mullins,
  • Emma M. Peacock,
  • Sander K. Haigh,
  • Carl J. Schiltz,
  • Clara Aicart-Ramos,
  • Miaw-Sheue Tsai,
  • David Cortez,
  • Fernando Moreno-Herrero,
  • Brandt F. Eichman

摘要

Replication fork reversal helps maintain genomic stability during replication stress. F-box helicase 1 (FBH1) catalyzes fork reversal and is an SCF (SKP-CUL1-F-box) E3 ubiquitin ligase that limits RAD51 association with chromatin. Here, we show that preferential binding of SCFFBH1 to the lagging strand template at DNA fork structures stimulates helicase activity and is required for fork reversal. A cryo-EM structure of SCFFBH1 bound to DNA representing a stalled fork reveals an intimate interaction between FBH1 and the fork junction. Disruption of this interface severely curtails fork reversal in vitro and replication progression in cells, providing a model for how ssDNA translocation by FBH1 facilitates annealing of parental DNA by a fundamentally different mechanism than the fork remodelers SMARCAL, HLTF, and ZRANB3. The structure provides a model for SCFFBH1 disassembly of RAD51 filaments through translocation and ubiquitination, and implies that RAD51 is associated with the lagging strand at stalled forks.