Cyclin-dependent kinase 1 is a highly conserved protein that functions as a serine/threonine kinase and is a key player in cell cycle regulation. It is encoded by the cdc28 and cdc2 genes in budding Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. In humans, Cdk1 is encoded by the CDC2 gene. Cdk1 forms a complex with its cyclin chaperone, which complex phosphorylates multiple target substrates (more than 75 have been identified in germinating yeast); phosphorylation of these proteins leads to cell cycle progression.

CDK1 and transcription programs

Unidirectional movement in the cell cycle is critical to cell viability and biological well-being. Reversing the direction of the cell cycle can have devastating consequences for cells, including genomic instability. As a result, cells have developed mechanisms to ensure that the cell cycle is irreversible. One of the main mechanisms that promotes unidirectionality involves regulating different transcription programs at different stages of the cell cycle. In general, each transcription program results in the expression of a proteome that performs processes important to the next stage of the cell cycle, thereby promoting one-way movement throughout the cell cycle. In addition, as we will discuss below, feedback mechanisms have been developed to ensure that the cell cycle is irreversible. Positive feedback loops ensure that cell cycle entry is robust and similar to a switch, while negative feedback loops inhibit the transcription process to prevent cell cycle reversal.

Figure 1. Protein structure of CDK1.

Cdk1 regulation

Upstream regulation of Cdk1 has been extensively reviewed, so we will only provide a more general overview of known information about Cdk1 regulation in Bacillus yeast. Cyclin and CDKs are well preserved between Saccharomyces cerevisiae and mammals. For example, human cyclin can replace germinated yeast cyclin, while human Cdc2 (Cdk1 in Saccharomyces cerevisiae) can replace Cdc2 in Schizosaccharomyces cerevisiae] and Cdk1 in Saccharomyces cerevisiae, indicating that evolution has maintained the cell cycle control. Cdk1 is inactive during G1 due to low cyclin concentrations and the presence of cyclin-dependent kinase inhibitors (CKI) Sic1 and Far1. When cyclin concentration increases and CKI is degraded, its activity increases in the late stage of G1. Cdk1 activity remained high until late, as cyclin was destroyed and CKIs were re-expressed, Cdk1 activity decreased. Decreased Cdk1 activity is essential for exiting mitosis and resets the cell cycle to a basic G1 state with low Cdk1 activity. As will be discussed later, fluctuations in Cdk1 activity play an important role in limiting DNA replication, repair, and isolation to specific stages of the cell cycle, and ensure the irreversibility of each stage of the cell cycle. The most important Cdk1 modulators are discussed below, although more proteins can affect Cdk1 activity to some extent.

CDK1 and DNA replication

The key result of the cell cycle is a complete and complete set of genetic material passed from one generation to the next. The key to faithfully performing this process lies in two events: (i) genome replication and (ii) the isolation of the replicated genome into daughter cells (we will discuss this in the "Cdk1 and chromosome segregation" section). In order to ensure that cells do not separate their genetic material before replication is complete, otherwise the genome will be unstable, the two processes must be separated in time. Chromosome replication occurs in the S phase, and separation of the replicated chromosomes occurs in the M phase. Cells have developed complex mechanisms that control the initiation of DNA replication and determine that DNA replication occurs only once per cell cycle, and Cdk1 plays a central role in these events.

Reference:

1. Farcas R; et al. Differences in DNA Methylation Patterns and Expression of the CCRK Gene inHuman and Nonhuman Primate Cortices., Mol Biol Evol, 2009, 26: 13791389.