Chapter 17: The Cell Cycle

The central role of cyclin-dependent kinases (Cdks) and their regulatory cyclin partners is explored, showing how specific cyclin-Cdk complexes trigger transitions between phases, such as G₁/S and G₂/M. The chapter explains how Cdk activity is modulated by phosphorylation, proteolysis, and binding to inhibitory proteins like p21 and p27. Cell cycle checkpoints are introduced as surveillance mechanisms that halt progression if DNA is damaged, replication is incomplete, or chromosome alignment is faulty. The roles of tumor suppressor proteins such as p53 are emphasized, particularly in response to genotoxic stress. Licensing of DNA replication origins ensures that replication occurs only once per cycle, with proteins like Cdc6 and the origin recognition complex (ORC) playing critical roles. The mitotic spindle assembly checkpoint guarantees that all chromosomes are properly attached to spindle microtubules before anaphase begins. The anaphase-promoting complex (APC/C), a ubiquitin ligase, is described as the key regulator of the metaphase-anaphase transition and mitotic exit. The chapter also discusses how external mitogenic signals and intracellular nutrient levels affect cell cycle entry via pathways like PI3K-Akt and MAPK. It concludes by highlighting the links between cell cycle misregulation and diseases such as cancer, as well as the utility of cell cycle regulators as targets for therapeutic intervention.