Czech scientists discover a cellular “safety switch” that protects DNA from damage

A research team led by Lukáš Čermák, in collaboration with Hana Polášek-Sedláčková’s group, has identified a previously unknown mechanism by which cells monitor the quality of DNA replication. When this control fails, the cell begins to replicate its DNA recklessly, leading to genome instability — a key early step in the development of cancer. The study was published on October 27, 2025, in the prestigious journal Nature Communications.

Whenever a cell divides, it must first copy its entire genetic code – billions of DNA “letters” — with extraordinary precision. Even minor errors or breaks in DNA can make the cell genetically unstable, a condition long associated with cancer formation.

New research conducted jointly by teams from the Institute of Molecular Genetics and the Institute of Biophysics of the Czech Academy of Sciences has described a previously unknown control step in DNA copying. The scientists found that the protein DCAF12 oversees the timing and quality of this process. Its job is to remove, at the right moment, a temporary “assembler” — a helper that puts together and delivers parts of the cell’s DNA-copying machinery into the nucleus — which then gets in the way if it stays. When this helper lingers, the cell rushes the job and errors accumulate.

DCAF12 gives the clean-up signal. Thanks to that, a six-subunit ring — the “motor” that opens DNA and enables accurate copying — can close properly. “When this checkpoint is missing, the temporary assembler isn’t cleared, replication runs under stress and DNA is damaged more often,” explains Lukáš Čermák of the Institute of Molecular Genetics of the Czech Academy of Sciences.

In other words: DCAF12 acts as a quality safeguard. It keeps DNA copying as accurate as possible. Without this safeguard, cells trade accuracy for speed — and such cells are more likely to become cancerous.

The research was supported by the Czech Science Foundation (GA ČR). Available clinical data suggest that DCAF12 function is associated with survival in women with ovarian cancer and in patients with lung cancer. Follow-up studies will therefore test the direct link between disruption of this control pathway, genomic instability, and tumor development.

Publication:
Anoop Kumar Yadav et al. CRL4⁽ᴰᶜᴬᶠ¹²⁾ regulation of MCMBP ensures optimal licensing of DNA replication. Nature Communications (2025). DOI: 10.1038/s41467-025-64258-5

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