Transcription-Replication Conflicts as a Source of Genome Instability

Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously act on the same DNA sequence. Conflicts between the replication and transcription machineries (transcription-replication conflicts, or TRCs) are widespread in both prokaryotes and eukaryotes and have the capacity to both cause DNA damage and compromise complete, faithful replication of the genome. This review will highlight recent studies investigating the genomic locations of TRCs and the mechanisms by which they may be prevented, mitigated, or resolved. We address work from both model organisms and mammalian systems but predominantly focus on multicellular eukaryotes owing to the additional complexities inherent in the coordination of replication and transcription in the context of cell type-specific gene expression and higher-order chromatin organization.

Automated summary

This review focuses on the conflicts between transcription and replication, known as transcription-replication conflicts (TRCs), and their impact on genome stability. Recent studies on the genomic locations of TRCs and the mechanisms to prevent or resolve them shed light on how cells regulate and protect DNA during replication and transcription.