Inside our bodies the cell cycle proceeds through G1, S, G2, and M phases. Hartwell, working with budding yeast, identified CDC genes and showed that each phase is guarded by “checkpoints.” Hunt used sea-urchin eggs to discover proteins called “cyclins,” whose levels rise and fall like the hands of a clock. Nurse isolated the cdc2 gene in fission yeast and proved that humans possess a homologous gene, demonstrating the cycle’s universal design. Together their work explained how cells detect DNA damage and halt division, and why that safety brake fails in cancer. Modern anti-cancer drugs such as CDK inhibitors owe much to these fundamental insights.

The cell cycle is a self-regulating system that synchronizes DNA replication and cell division. Hartwell used temperature-sensitive mutants in budding yeast to identify numerous CDC genes, including cdc28, and articulated the G1/S checkpoint concept. Hunt demonstrated that cyclins A and B undergo synthesis and ubiquitin-mediated degradation, acting as a molecular timer and popularizing the term “cyclin.” Nurse cloned fission-yeast cdc2, then identified human CDK1 via functional complementation, proving that cyclin-CDK complexes are a universal engine. Phosphorylation-dependent CDK regulation and APC/C-driven cyclin destruction were shown to provide irreversibility and directionality to the cycle. These advances spread into cancer biology, developmental biology, aging research, and antitumor drug design, offering an integrated molecular framework for cell proliferation.

Hartwell identified cdc28, the core CDK, and the RAD9-mediated checkpoint pathway through complementation cloning of temperature-sensitive cdc mutants in S. cerevisiae. Hunt isolated M-phase-specific cyclin B from Paracentrotus lividus egg extracts using 35S-methionine pulse labeling and demonstrated APC/C-dependent K48 polyubiquitination leading to its rapid degradation. Nurse exploited the S. pombe cdc2 arrest phenotype and HeLa cDNA libraries to clone human CDK1, revealing evolutionary conservation of the CDK network. The molecular logic of cycle control—Wee1/Cdc25-regulated T14/Y15 phosphorylation, Start regulation by Cln-Cdc28, and Chk1/Chk2-mediated DNA damage responses—was consequently systematized. These insights directly informed elucidation of the Rb-E2F axis and the development of selective CDK4/6 inhibitors such as palbociclib, exerting multilayered impact on transcriptional regulation, chromosome dynamics, and cancer therapy strategies.