Preventing replication stress to maintain genome stability: resolving conflicts between replication and transcription

Area of Science:

• Molecular Biology
• Genetics
• Genomics

Background:

• DNA and RNA polymerases compete for genomic DNA templates, leading to potential conflicts.
• Cells possess mechanisms to prevent and resolve interference between replication and transcription.
• Replication-transcription conflicts can impact gene expression, epigenetic memory, and genome stability.

Purpose of the Study:

• To review the structural and regulatory aspects of replication-transcription clashes.
• To discuss the influence of cotranscriptional processes on replication fork integrity.
• To explore the consequences of uncoordinated processes, including fork reversal and R-loop formation.

Main Methods:

• Review of existing literature on replication-transcription conflicts.
• Analysis of the topology and architecture at clash sites.
• Discussion of regulatory circuits governing replication fork passage.

Main Results:

• Replication fork clashes with transcription bubbles involve specific topologies and architectures.
• Cotranscriptional processes like mRNA splicing and export affect replication fork integrity.
• Uncoordinated processes can lead to fork reversal, R-loop formation, and genome instability.

Conclusions:

• Proper coordination of replication and transcription is crucial for genome integrity.
• Replication fork passage may reset epigenetic landscapes and influence transcriptional memory.
• Replication-transcription conflicts have evolutionary implications and can contribute to oncogenic stress.