Cancer researchers at the University of Chicago and the University of California, San Francisco (UCSF) have discovered that mutations in certain genes can lead to the accumulation of DNA errors, resulting in a specific type of genetic change known as large tandem duplications (TDs) that can arise from the collision of two critical cellular processes: transcription and DNA replication. Understanding the specific type of DNA damage that leads to TDs may open new avenues for developing treatments targeting cancers with these specific genetic alterations. The study findings were published in Nature Cancer in November 2024.
DNA acts as a master copy of genetic information and must therefore remain consistent and error-free as cells divide and multiply across generations. The reliability of the DNA replication process depends on genome stability, which is maintained by DNA repair mechanisms that correct any mistakes that occur during DNA replication. Failures in these repair systems can introduce mutations and, ultimately, create genomic instability, which is strongly linked to cancer development.
However, the underlying causes of such failures are not yet fully understood. DNA consists of two strands in a double-helix structure. Each strand serves two primary purposes: acting as a template during DNA replication and providing instructions for protein synthesis in a process called transcription.
Replication and transcription machinery can operate simultaneously on the same DNA mole.