Transcription-mediated replication hindrance: a major driver of genome instability

Genes Dev. 2019 Aug 1;33(15-16):1008-1026. doi: 10.1101/gad.324517.119. Epub 2019 May 23.


Genome replication involves dealing with obstacles that can result from DNA damage but also from chromatin alterations, topological stress, tightly bound proteins or non-B DNA structures such as R loops. Experimental evidence reveals that an engaged transcription machinery at the DNA can either enhance such obstacles or be an obstacle itself. Thus, transcription can become a potentially hazardous process promoting localized replication fork hindrance and stress, which would ultimately cause genome instability, a hallmark of cancer cells. Understanding the causes behind transcription-replication conflicts as well as how the cell resolves them to sustain genome integrity is the aim of this review.

Keywords: DNA–RNA hybrids; chromosome fragility; genetic instability; replication fork stalling; transcription.

Publication types

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

MeSH terms

  • DNA Replication / physiology*
  • Genome / genetics
  • Genomic Instability / genetics*
  • Humans
  • Neoplasms / physiopathology
  • Transcription Elongation, Genetic / physiology
  • Transcription, Genetic / physiology*