# The Less Known Cyclins--Uncovered
## 3 Cyclin F
The absence of NuSAP leads to incorrect spindle formation, erroneous segregation of chromosomes and eventually blocks cell proliferation, whereas an increased level of NuSAP results in mitotic arrest and microtubule formation. Cyclin F helps to control the amount of NuSAP and therefore is essential for proper cell division. Considering all of the above, defective cyclin F may contribute to the formation of the hypermutator phenotype and chromosomal instability through the RRM2, CP110 and NuSAP pathways [22; 26]. In the case of DNA damage, the cell activates specific checkpoints to stop proliferation and facilitate DNA repair. Cyclin F in normal cells inhibits the activity of the Mpb-related protein B (B-Myb) transcription factor. [PERSON] et al., 2015 [27] performed screening tests for RNA interference involved in ubiquitination processes. Their results show that in normal cells that were not exposed to ionizing radiation (IR) B-Myb-dependent control of cyclin F has little effect on the activation of the transcription process and proliferation of cells. Moreover, in the cells damaged by IR exposition, cyclin F inhibits the activity of B-Myb in the aim to trigger the G2 phase checkpoint. It is, therefore, possible that cyclin F plays an important role in the development of cancer by preventing genomic instability and excessive cell proliferation by B-Myb suppression [27]. Another function of cyclin F in normal cells is its participation in embryogenesis. [PERSON] et al, 2004 [28]. investigated the role of cyclin F in in vitro and in vivo conditions. For the study, they created mice with complete or conditional deficiency of cyclin F (CycF\(-/-\)) and cyclin F-negative MEF. CycF\(-/-\) embryos showed a wide range of  
Figure 2: The cyclin F–RRM2 axis is essential for genome stability and DNA repair. The defective elimination of RRM2 drives to elevated DNA pool and increases the cell capability to DNA repair. This can lead to uncontrolled proliferation and drug resistance. problems and developmental defects like lack of complete axial rotation, delay in neural tube closure and delayed brain formation, together with abnormal development of the yolk sac and chorioallantoic placentation. In turn, CycF\(-\) / \(-\) MEF allowed for assessing the defects in the cell cycle caused by the lack of cyclin F function. The result showed that cyclin F is not the essential factor in the context of MEF viability, but it affects their cell cycle. The cells were characterized by the decreased proliferation rate, slightly altered cell cycle distribution and delayed cell cycle re-entry after the serum starvation [28]. Furthermore, appropriate expression and location of cyclin F play a major role in cell differentiation and carcinogenesis. [PERSON] et al., 2013 [PERSON] et al. (2013) showed that the reduction in cyclin F expression is associated with unfavorable prognosis for patients with liver cancer. Decreased expression of cyclin F in poorly differentiated hepatocellular carcinoma (HCC) may contribute to the tumorigenesis and HCC progression. The results confirmed that cyclin F is an independent prognostic marker for the overall survival of patients with liver cancer. Moreover, decreased expression of cyclin F correlated with the size of the tumor, alpha-fetoprotein level in serum and tumor multiplicity. Another way of cyclin F contribution to the maintenance of genomic stability is the reduction of centrophore duplication abnormalities, which additionally proves that a decrease in the level of cyclin F may lead to tumor initiation and progression [PERSON] et al. (2013). Under normal conditions, cyclins have clear subcellular localization patterns. For example, cyclin A in normal cells is located mainly in the nucleus, while in tumor cells, increased translocation to the cytoplasm is observed [30]. The presence of cyclin F was at first confirmed only in the cell nucleus, but later it was also localized in the cytoplasm, where it interacts with y-tubulin [24]. [PERSON] et al., 2012 [PERSON] et al.