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<p>Replication fork collapse at single-strand DNA breaks threatens genome stability but how such forks are repaired and resolved has remained unclear. Here we replicate site-specific nicks with single or converging replication forks in <i>Xenopus</i> <i>laevis</i> egg extracts. Collapse of a single fork generates a single-ended double-strand break (DSB) that undergoes homologous recombination to yield stable D-loops and end-to-end fusions, yet does not restart DNA synthesis. Single collapsed forks can also undergo extensive nucleolytic degradation, appearing to disassemble the sister fork through ‘secondary collapse’ events that resolve single-ended DSBs without engaging DSB repair. In contrast, semisynchronous convergent collapse generates a double-ended DSB that is primarily repaired through annealing-dependent DSB repair, completing DNA synthesis but generating precise deletions and templated insertions. These error-prone products are not detected following single-fork collapse. Our findings demonstrate that single and semisynchronous convergent collapsed forks elicit distinct repair outcomes.</p>

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Distinct repair outcomes from single and convergent replication fork collapse

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月27日

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  • Sara C. Conwell,
  • Khushi V. N. Patel,
  • Savannah J. Weeks-Pollenz,
  • Steven N. Dahmen,
  • Matthew T. Cranford,
  • William G. Dunphy,
  • David T. Long,
  • David Cortez,
  • James M. Dewar

摘要

Replication fork collapse at single-strand DNA breaks threatens genome stability but how such forks are repaired and resolved has remained unclear. Here we replicate site-specific nicks with single or converging replication forks in Xenopus laevis egg extracts. Collapse of a single fork generates a single-ended double-strand break (DSB) that undergoes homologous recombination to yield stable D-loops and end-to-end fusions, yet does not restart DNA synthesis. Single collapsed forks can also undergo extensive nucleolytic degradation, appearing to disassemble the sister fork through ‘secondary collapse’ events that resolve single-ended DSBs without engaging DSB repair. In contrast, semisynchronous convergent collapse generates a double-ended DSB that is primarily repaired through annealing-dependent DSB repair, completing DNA synthesis but generating precise deletions and templated insertions. These error-prone products are not detected following single-fork collapse. Our findings demonstrate that single and semisynchronous convergent collapsed forks elicit distinct repair outcomes.