Researchers at LUMC have identified that the CFAP20 protein functions as a 'traffic controller' on DNA, a discovery published in the journal Nature.
DNA processes involve two types of molecular 'trains': replication, which copies DNA for cell division, and transcription, which reads DNA to produce mRNA. These processes occur simultaneously, with polymerases traveling at speeds of one to two thousand base pairs per minute. Collisions often occur when the transcription train starts slowly at the beginning of a gene, while the faster replication train follows behind.
The CFAP20 protein facilitates the acceleration of the transcription train, preventing it from being hit by the replication train. Without CFAP20, transcription trains stall, blocking the DNA track and leading to collisions with replication trains. This disruption results in about half of replication processes stopping, while others accelerate to compensate, producing 'bad copies' of DNA.
These faulty DNA copies can lead to uncontrolled cell division or incorrect cellular instructions, which may contribute to the development of cancer over time. Although CFAP20 was previously known, its function within the cell nucleus was not understood until this study.
The research was a collaborative effort between the fields of replication and transcription, which traditionally operated separately. This collaboration allowed for the observation of how replication and transcription processes interact.
The findings do not immediately translate to treatments but establish a foundation for future clinical applications. For cancer biologists, the study provides additional insight into cellular deregulation leading to cancer. For drug developers, CFAP20 represents a new potential target, as tumor cells appear to depend on it for faster division, even if it compromises DNA quality. The study also highlights the value of fundamental research into less-studied genes and proteins.