Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells

Replication fork reversal protects forks from breakage after poisoning of Topoisomerase 1. We here investigated fork progression and chromosomal breakage in human cells in response to a panel of sublethal genotoxic treatments, using other topoisomerase poisons, DNA synthesis inhibitors, interstrand cross-linking inducers, and base-damaging agents. We used electron microscopy to visualize fork architecture under these conditions and analyzed the association of specific molecular features with checkpoint activation. Our data identify replication fork uncoupling and reversal as global responses to genotoxic treatments. Both events are frequent even after mild treatments that do not affect fork integrity, nor…

• NS
  National Science Foundation
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Award: 31003A_146924
• UZ
  Universität Zürich
• NI
  National Institutes of Health

  Award: R01GM108648