The Replication Stress Response on a Narrow Path Between Genomic Instability and Inflammation

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Eukaryotic DNA replication during S phase involves thousands of replisomes at fragile replication forks.
• Coordinated action of numerous enzymes is crucial for accurate DNA replication from origin licensing to termination.

Purpose of the Study:

• To review mechanisms ensuring DNA replication completion under challenging conditions.
• To cover new findings on stalled fork processing and its link to cellular responses.

Main Methods:

• Review of existing literature on DNA replication, fork stability, and DNA damage response pathways.
• Analysis of recent studies investigating the consequences of stalled replication fork repair.

Main Results:

• Stalled replication fork processing can release DNA fragments into the cytoplasm.
• Cytoplasmic DNA fragments activate the cGAS-STING pathway, initiating an inflammatory response.

Conclusions:

• DNA damage and replication fork repair can activate inflammatory pathways with dual effects on stressed cells.
• These findings have significant implications for understanding interferonopathies and developing novel cancer treatments.