Researchers led by Oncode Investigator Nitika Taneja have uncovered how cells reorganise the structure of their DNA to protect it when replication is disrupted. The findings, published in Nature, provide new insight into a fundamental process that helps maintain genome stability.
Copying DNA is one of the most essential processes in life, but it is also one of the most vulnerable. DNA damage, a shortage of building blocks or certain cancer treatments can interrupt replication, leaving newly copied DNA exposed.
The research team found that cells respond by temporarily reshaping the three-dimensional organisation of their DNA. They discovered that chromatin loops become stabilised around the sites where DNA replication has slowed or stalled, creating a protective environment that helps prevent newly copied DNA from being degraded.
Using advanced 3D-genome mapping, single-cell sequencing, imaging and single-molecule approaches, the researchers showed that disrupting this protective mechanism makes newly replicated DNA more vulnerable to damage. Their findings also suggest that defects in this process may contribute to increased genome instability in cancers with impaired DNA repair, including BRCA2-deficient tumours.
Nitika Taneja, Oncode Investigator at Erasmus MC
"When DNA copying stalls, cells do more than call in repair proteins – they reshape the genome itself. We found that cells stabilise chromatin loops around vulnerable newly copied DNA, creating a protective space that shields it from degradation. This gives us a new way to think about genome stability: not only as a question of repair proteins, but also as a question of how the genome is folded in space".
The study reveals an unexpected role for the three-dimensional organisation of the genome in protecting DNA during replication. By showing how cells respond to replication stress, the findings provide a new perspective on the mechanisms that help preserve genome stability and offer a valuable foundation for future cancer research.
Read the publication in Nature.