Cyclin F has been discovered for over two decades. Its starts to accumulate from S phase, reaches peak level at G₂ phase and is abruptly degraded in late mitosis. Unlike other cyclins with similar cell cycle kinetics (i.e. cyclin A, cyclin B), no CDK partner has been identified for cyclin F. Cyclin F has a high turnover rate due to a PEST sequence at its C-terminus. Cyclin F is essential for early mouse embryo development and mutations of cyclin F are found in human amyotrophic lateral sclerosis. Therefore, cyclin F has been regarded as a non-canonical cyclin that may not be involved in cell cycle control. Biochemically, cyclin F is best known as the substrate binding subunit of a ubiquitin ligase, the SKP1-CUL1-F-box protein (SCF) complex. A clear role of cyclin F in the regula...[ Read more ]

Cyclin F has been discovered for over two decades. Its starts to accumulate from S phase, reaches peak level at G₂ phase and is abruptly degraded in late mitosis. Unlike other cyclins with similar cell cycle kinetics (i.e. cyclin A, cyclin B), no CDK partner has been identified for cyclin F. Cyclin F has a high turnover rate due to a PEST sequence at its C-terminus. Cyclin F is essential for early mouse embryo development and mutations of cyclin F are found in human amyotrophic lateral sclerosis. Therefore, cyclin F has been regarded as a non-canonical cyclin that may not be involved in cell cycle control. Biochemically, cyclin F is best known as the substrate binding subunit of a ubiquitin ligase, the SKP1-CUL1-F-box protein (SCF) complex. A clear role of cyclin F in the regulation of cell cycle progression in somatic cells is not fully elucidated. To further explore potential functions of cyclin F in cell cycle regulation, I established cyclin F knock-out (KO) cell lines in the haploid cell line HAP1 cells using CRISPR/Cas9 system. Using cyclin F-KO cells, I confirmed that disruption of cyclin F did not affect the profile of normal cell cycle. But long-term survival rate after ionizing radiation (IR) exposure was reduced in cyclin F-depleted cells compared to parental (wild type) cells. It was reported that cyclin F level is reduced after IR exposure by an ATR-dependent mechanism. I further demonstrated that the IR-induced decrease of cyclin F was transient degradation and restricted to S phase. Since cyclin F responded to IR in such a cell cycle-dependent manner, I also investigated if cyclin F was involved in IR-induced DNA damage response. Although cyclin F depletion did not influence the activation of the DNA damage response, recovery from IR-mediated 53BP1 foci formation was accelerated. Furthermore, live-cell-imaging analysis revealed that in the absence of cyclin F, cells were very likely to acquire an elongated mitosis after IR exposure. Collectively, these results suggested that cyclin F might play a role in cellular response to DNA damage.