The long and short of CDK12
Mutations in the BRCA1 and BRCA2 genes pose a serious risk for breast and ovarian cancer because they endanger the genomic stability of a cell by interfering with homologous recombination repair (HR), a key mechanism for accurately repairing harmful double-stranded breaks in DNA. Without the ability to use HR to fix double-stranded breaks, the cell is forced to resort to more error-prone — and thus more cancer-prone — forms of DNA repair. The BRCA1 and BRCA2 genes are not the only genes whose mutations foster tumorigenesis by causing an inability to repair DNA double strand breaks by HR. Mutations in twenty-two genes are known to disrupt HR, giving rise to tumors with what researchers call “BRCAness” characteristics. All but one of these BRCAness genes are known to be directly involved in the HR pathway. The one exception, CDK12, is thought to facilitate a set of different processes altogether, involving how RNA transcripts are elongated, spliced...