The impact of replication stress on replication dynamics and DNA damage in vertebrate cells

Nat Rev Genet. 2017 Sep;18(9):535-550. doi: 10.1038/nrg.2017.46. Epub 2017 Jul 17.


The interplay between replication stress and the S phase checkpoint is a key determinant of genome maintenance, and has a major impact on human diseases, notably, tumour initiation and progression. Recent studies have yielded insights into sequence-dependent and sequence-independent sources of endogenous replication stress. These stresses result in nuclease-induced DNA damage, checkpoint activation and genome-wide replication fork slowing. Several hypotheses have been proposed to account for the mechanisms involved in this complex response. Recent results have shown that the slowing of the replication forks most commonly results from DNA precursor starvation. By concomitantly increasing the density of replication initiation, the cell elicits an efficient compensatory strategy to avoid mitotic anomalies and the inheritance of damage over cell generations.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cells / metabolism
  • DNA Damage*
  • DNA Replication*
  • Deoxyribonucleotides / metabolism
  • Humans
  • Nucleic Acid Conformation
  • Transcription, Genetic


  • Deoxyribonucleotides