Altered expression of cell cycle genes

The eukaryotic cell cycle is divided into phases, comprising the interphase (G1, S, and G2) and the mitotic (M) phase. Under certain conditions, cells can exit the cycle and reversibly enter a state of quiescence (the G0 phase), terminally differentiate or enter a senescent state (Kumari and Jat 2021).

During cell division, the cells can progress through the cycle if they pass three major checkpoints (in G1-to-S, G2-to-M and M-to-G1), which ensure that the resulting daughter cells are healthy. The passage through successive phases is driven by cyclins and cyclin-dependent kinase (CDK) complexes (Murray, 2004). Cyclins are divided into 4 groups (A-, B-, D-, and E-cyclins) and CDKs include at least 11 proteins (Murray, 2004; Hochegger et al., 2008; Malumbres, 2009). However, there are two different perspectives as to how the cyclin-Cdk complexes temporally regulate events during the cell cycle (Hochegger et al., 2008). One model asserts that the correct completion of the S and M phases is brought about through different biochemical activities of cyclin-cdk heterodimers associated with each phase. In this view, the various cyclin-CDK complexes appear in a specific temporal sequence and target different substrates to drive progression through the cell cycle (van den Heuvel and Harlow, 1993; Sherr, 1993; Pagliuca et al., 2011). On the other hand, a second model proposes that it is the progressive increase in total CDK cell activity that drives the cell cycle, rather than CDK substrate specificity. In this view, substrates in the DNA replication phase are phosphorylated at a lower total CDK activity level than substrates in the mitotic phase (Swaffer et al., 2016). Recently, Basu et al., have reconciled these two opposing perspectives into a unitary framework which proposes a quantitative view of core CDK cell cycle control with a minor qualitative element (Basu et al., 2022). Using phosphoproteomics to study in vivo CDK activity in fission yeast, the authors show that cyclin-CDK complexes are not completely specialised for either S or M phase, and that increasing the CDK activity of S phase dimers is sufficient to carry out mitosis (Basu et al., 2022).

How it is measured or detected

Expression of cyclins and Cdks at various phases of the cell cycle can be performed at the transcript or protein level. The mRNA content of specific cyclins and Cdks can be measured using qPCR, or in the context of a more global analysis using microarray or RNAseq methods (see for e.g. Karsten et al., 2003; Kowalczyk et al., 2015; Cheroni et al., 2022). The protein amount of individual Cdks, cyclins, as well as their phosphorylated forms can be detected using immunodetection methods such as western blotting or enzyme-linked immunosorbent assays (ELISAs), as well as through mass spectrometric approaches (see for e.g. Frisa and Jacobberger, 2009; Basu et al., 2022).

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