DNA damage responses that enhance resilience to replication stress

Kazumasa Yoshida, Masatoshi Fujita

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


During duplication of the genome, eukaryotic cells may experience various exogenous and endogenous replication stresses that impede progression of DNA replication along chromosomes. Chemical alterations in template DNA, imbalances of deoxynucleotide pools, repetitive sequences, tight DNA–protein complexes, and conflict with transcription can negatively affect the replication machineries. If not properly resolved, stalled replication forks can cause chromosome breaks leading to genomic instability and tumor development. Replication stress is enhanced in cancer cells due, for example, to the loss of DNA repair genes or replication–transcription conflict caused by activation of oncogenic pathways. To prevent these serious consequences, cells are equipped with diverse mechanisms that enhance the resilience of replication machineries to replication stresses. This review describes DNA damage responses activated at stressed replication forks and summarizes current knowledge on the pathways that promote faithful chromosome replication and protect chromosome integrity, including ATR-dependent replication checkpoint signaling, DNA cross-link repair, and SLX4-mediated responses to tight DNA–protein complexes that act as barriers. This review also focuses on the relevance of replication stress responses to selective cancer chemotherapies.

Original languageEnglish
Pages (from-to)6763-6773
Number of pages11
JournalCellular and Molecular Life Sciences
Issue number21-22
Publication statusPublished - Nov 2021

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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