Background
Cyclin-dependent kinase 12 is composed of a central CTD kinase domain, several proline-rich regions, and several amino-terminal arginine/serine motifs common to splicing factors. CDK12 is ubiquitously expressed and forms a complex with cyclin K that regulates phosphorylation of the C-terminal domain of RNA polymerase II. CDK12 is important for expression of a subset of long genes with high numbers of exons including some regulators of the DNA damage response, such as breast and ovarian cancer type 1 susceptibility protein 1 and ataxia telangiectasia and Rad3-related. Depletion of CDK12 results in spontaneous DNA damage and increased sensitivity to DNA damage agents. Research studies have shown that CDK12 is recurrently mutated in high-grade ovarian cancer. In addition, high levels of CDK12 are required to maintain pluripotency of embryonic stem cells.
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