To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

Internal regulatory checkpoints ensure that a cell’s size, energy reserves, and DNA quality and completeness are sufficient to advance through the cell cycle. At these checkpoints, positive and negative regulators promote or inhibit a cell’s continuation through the cell cycle.

Positive regulators include two protein groups that allow cells to pass through regulatory checkpoints: cyclins and cyclin-dependent kinases (CDKs). These proteins are present in eukaryotes, ranging from yeast to humans.

Cyclins can be categorized as G₁, G₁/S, S, or M cyclins based on the cell cycle phase or transition they are most involved in. Generally, levels of a given cyclin are low during most of the cell cycle but abruptly increase at the checkpoint they most contribute to (G₁ cyclins are an exception, as they are required throughout the cell cycle). The cyclin is then degraded by enzymes in the cytoplasm and its levels decline. Meanwhile, cyclins needed for the next checkpoints accumulate.

To regulate the cell cycle, cyclins must be bound to a Cyclin-dependent kinase (CDK)—a type of enzyme that attaches a phosphate group to modify the activity of a target protein. The CDK is only active when bound to a cyclin. Depending on the cyclin they are bound to, CDKs are directed to different target proteins that are needed to advance to a particular cell cycle stage.

Compared to cyclins, CDKs remain at relatively constant levels throughout the cell cycle. However, their activity and the proteins they target change according to varying levels of cyclins across the cell cycle.