[HTML][HTML] Ovarian cancer-associated mutations disable catalytic activity of CDK12, a kinase that promotes homologous recombination repair and resistance to cisplatin …

PM Joshi, SL Sutor, CJ Huntoon, LM Karnitz - Journal of Biological …, 2014 - ASBMB
Mutations in the tumor suppressors BRCA1 and BRCA2, which encode proteins that are key
participants in homologous recombination (HR) repair, occur in∼ 20% of high grade serous
ovarian cancers. Although only 20% of these tumors have mutations in BRCA1 and BRCA2,
nearly 50% of these tumors have defects in HR. Notably, however, the underlying genetic
defects that give rise to HR defects in the absence of BRCA1 and BRCA2 mutations have
not been fully elucidated. Here we show that the recurrent somatic CDK12 mutations …