# The Less Known Cyclins--Uncovered
## 8 Cyclin K  
Cyclin K is a cell cycle protein. In humans, it is encoded by the CCNK gene, which can be found on chromosome 14q32.2. The protein is the most closely related to human cyclins C and H, which are members of the transcriptional cyclin family. The gene encoding human cyclin K was first isolated as a restoration of cell cycle progression (CPR) due to its participation in shaping the phenotype of the yeast Saccharomyces cerevisiae [67, 68]. It also can limit lethality due to the deletion of the G1 cyclin genes, such as Ceroid-Lipofuscinos, Neuronal 1 (CLN1), Ceroid-Lipofuscinos, Neuronal 2 (CLN2) and Ceroid-Lipofuscinos, Neuronal 3 (CLN3) [68]. Cyclin K binds to several cyclin-dependent kinases: Cdk9, Cdk12 and Cdk13, and activates them [69, 70].  
Cyclin K was initially considered as an alternative Cdk9 subunit [69]. However, later studies showed that it also binds to Cdk12 and Cdk13 (Figure 3). Both complexes (cyck-Cdk12 and cyck-Cdk13) are involved in the regulation of the transcription process but on different principles. They regulate transcription and post-transcriptional mRNA modifications by phosphorylation of the CTD of RNAPII and other transcription regulators, like negative extension factor (NELF), 5,6-dichloro-1-D-ribofuranosylbenzimidazole (DRB) or DRB sensitivity inducing factor (DSIF) [70]. Additionally, [PERSON] et al., 2002 [67] showed that cyclin K activates the transcription process only when it is attached to RNA, suggesting that cyck-Cdk9 may be required by RNA-related proteins to their transcriptional activity [71]. However, [PERSON] et al., 2002 [71] suggest that the cyclin K gene may be activated by a transcription factor with p53 tumor suppressor properties after treatment with adriamycin, ultraviolet radiation or gamma radiation [67, 69, 71]. The p53 protein is involved in the regulation of many cellular processes, in particular the activation of DNA repair mechanisms, regulation of the cell cycle and the induction of apoptosis in response to DNA damage [67].  
The transcription regulators of the Cdk and cyclin families also participate in DNA repair and genome stability. [PERSON] et al., 2012 [70] showed that the expression of several DNA damage response genes, including some key players involved in maintaining genomic stability, depends on cyck-Cdk12. At least for breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia and Rad3-related protein (ATR) and Fanconi anemia, complementation group I (FANCI) regulation is at the transcriptional level. Cells that did not contain the cyck-Cdk12 induced spontaneous signaling of DNA damage as was indicated by the accumulation of 53 BP1 and \(\gamma\)-H2 AX outbreaks and an increased number of cells in the G2/M phase. Cells depleted of cyck-Cdk12 were sensitive to various DNA damaging factors, including camptothecin, mitomycin C and etoposide [72]. This sensitivity of the cells to various types of DNA damage is consistent with the proposed role of this complex in the DDR pathway and maintaining genomic stability [72, 73].  
In tumor cells, it is suggested that cyclin K can be a prognostic marker. Works of [PERSON] et al., 2017 [74] revealed that the depletion of cyclin K in prostate cancer cells results in apoptosis and inhibits tumor cell proliferation, which is caused by the cell cycle arrest in the G2/M phase. It was also shown that cyclin K, by regulating Aurora B kinase, causes cell cycle block and apoptotic cell death by inducing a mitotic catastrophe in prostate cancer cells [74].