Professor Ulrich Rass

Since its discovery 30 years ago, scientists have puzzled over why the enzyme DNA2 is essential in human cells and how its functions relate to disease.

Researchers at Sussex’s Genome Damage and Stability Centre (GDSC) have now provided strong evidence that DNA2 acts as a “gatekeeper” when DNA replication – the process of copying our genetic code – gets stuck.

Their paper, published in Nature, shows that without DNA2, cells turn to a backup system.

That system relies on recombination, a process best known for enhancing diversity by shuffling genetic material. While helpful in small doses, too much recombination creates harmful DNA structures that can cause cells to deteriorate and lead to growth impairment.

Co-author Professor Ulrich Rass said: “This is a breakthrough because the findings open a new perspective on the interplay of DNA replication and DNA recombination.

“It provides a first consistent explanation for the underlying molecular pathology and reveals how patient mutations in DNA2 result in dwarfism.

“It also helps explain why many cancers overexpress DNA2: it protects tumour cells from the high levels of stress they face when copying DNA.”

The GDSC team used cutting-edge CRISPR technology and advanced microscopy to reveal DNA2’s true role. Their discovery opens new possibilities for therapies – from understanding genetic disorders to exploring whether blocking DNA2 could make cancer cells more vulnerable.

'DNA2 enables growth by restricting recombination-restarted replication' is published in Nature.