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.
[1] Ko, T.K. et al. (2001) J Cell Sci 114, 2591-603.
[2] Bartkowiak, B. et al. (2010) Genes Dev 24, 2303-16.
[3] Blazek, D. et al. (2011) Genes Dev 25, 2158-72.
[4] Cheng, S.W. et al. (2012) Mol Cell Biol 32, 4691-704.
[5] The Cancer Genome Atlas Research Network (2011) Nature 474, 609-15.
[6] Carter, S.L. et al. (2012) Nat Biotechnol 30, 413-21.
[7] Dai, Q. et al. (2012) J Biol Chem 287, 25344-52.
