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

Abstract

In this review, Gómez-González et al. discuss the underlying causes of transcription–replication conflicts, which are major threats to genome integrity. They also discuss mechanisms by which cells resolve these conflicts to sustain genome integrity.

Abstract

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.