Reactome | CDK12 phosphorylates RNA Pol II CTD at DNA repair genes

CDK12 phosphorylates RNA Pol II CTD at DNA repair genes

Stable Identifier

R-HSA-6797606

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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CDK12 phosphorylates RNA Pol II CTD at DNA repair genes

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CDK12, in complex with CCNK (cyclin K), phosphorylates heptapeptide repeats in the C-terminal domain (CTD) of the RNA polymerase II (RNA Pol II) subunit POLR2A. CDK12 may require phosphorylation of its threonine residue T893 to achieve full catalytic activity, but the activating kinase is not known. CDK12-mediated phosphorylation of the CTD of POLR2A occurs after the heptapeptide repeats in the CTD of POLR2A undergo phosphorylation by the CDK9-containing P-TEFb complex. It is unclear whether CDK12 acts on the second serine or the fifth serine or both in the YSPTSPS repeats. The mammalian POLR2A contains 52 heptapeptide repeats that start at amino acid position 1615. The exact localization of CDK9 and CDK12 target sites relative to the full-length POLR2A is not known. CDK12-mediated phosphorylation of the pre-phosphorylated RNA Pol II complex is important for the transcription of a group of genes with long and complex structures, involved in DNA repair (Blazek et al. 2011, Cheng et al. 2012, Bosken et al. 2014, Bartkowiak and Greenleaf 2015, Liang et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
25429106	Expression, purification, and identification of associated proteins of the full-length hCDK12/CyclinK complex Bartkowiak, B, Greenleaf, AL	J. Biol. Chem.	2015
24662513	The structure and substrate specificity of human Cdk12/Cyclin K Merzel Schachter, M, Geyer, M, Eick, D, Vogel-Bachmayr, K, Blazek, D, Farnung, L, Anand, K, Bösken, CA, Fisher, RP, Hintermair, C	Nat Commun	2014
25561469	Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing Liang, K, Smith, E, Florens, LA, Shilatifard, A, Gilmore, JM, Gao, X, Washburn, MP	Mol. Cell. Biol.	2015
22988298	Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for the phosphorylation of the C-terminal domain of RNA polymerase II Kuzyk, MA, Vollett, SE, Tien, JF, Ichu, TA, Cheng, SW, Chang, VC, Marra, MA, Griffith, M, Moradian, A, Morin, GB	Mol. Cell. Biol.	2012
22012619	The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes Cimermancic, P, Johansen, E, Ule, J, Peterlin, BM, Hulinkova, P, Luo, Z, Blazek, D, Kohoutek, J, Bartholomeeusen, K	Genes Dev.	2011