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The regulation of the cell cycle

By Seán Mac Fhearraigh and David Bruce

The cell cycle is the coordinated division of a cell into two genetically identical daughter cells. Work over the past forty years has revealed the molecular components that control the eukaryotic cell cycle.


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Pioneering work by Paul Nurse and Leland Hartwell identified genetic mutants that regulate cell cycle progression in Saccharomyces pombe and Saccharomyces cerevisiae respectively. Furthermore, the discovery of maturation-promoting factor in Xenopus laevis by Yoshio Masui together with the identification of cyclins in sea urchin eggs by Tim Hunt led to the discovery of key components that regulate the cell cycle. In 2001, Paul Nurse, Leland Hartwell and Tim Hunt received the Nobel prize in physiology or medicine for their contribution to the understanding of cell cycle regulation (Pulverer, 2001).

The mammalian cell cycle can be divided into the four distinct phases Gap 1 (G1), synthesis (S), Gap 2 (G2) and mitosis (M phase) which require three ‘switch-like’ transitions to regulate S phase entry, mitotic entry and the exit of mitosis (Hochegger et al., 2008). Mitosis is subdivided into a further six phases including prophase, pro-metaphase, metaphase, anaphase, telophase and cytokinesis which control nuclear envelope breakdown (NEBD), the attachment of chromosomes to spindle poles, the alignment of chromosomes upon the metaphase plate, the separation of sister chromatids and the separation of the cell into two daughter cells respectively.

Cyclin-dependent kinases (Cdks) are Ser/Thr kinases that regulate cell cycle progression in combination with temporal cyclin binding partners. There are four Cdk family members (Cdk2, Cdk3, Cdk4 and Cdk6) that regulate interphase in combination with their cyclin binding partners (cyclin D, cyclin E and cyclin A).


References

  • Hochegger HS, Takeda S, Hunt T (2008). Cyclin-dependent kinases and cell cycle transitions: does one fit all? Nat Rev Mol Cell Biol 9, 910–916
  • Pulverer, B (2001). Trio united by division as cell cycle clinches centenary Nobel. Nature 413, 553

The cell cycle is the coordinated division of a cell into two genetically identical daughter cells. Work over the past forty years has revealed the molecular components that control the eukaryotic cell cycle. Pioneering work by Paul Nurse
and Leland Hartwell identified genetic mutants that regulate cell cycle progression in Saccharomyces pombe and S. cerevisiae respectively.
Furthermore, the discovery of maturation-promoting factor in Xenopus laevis by
Yoshio Masui together with the identification of cyclins in sea urchin eggs by Tim
Hunt led to the discovery of key components that regulate the cell cycle. In 2001,
Paul Nurse, Leland Hartwell and Tim Hunt received the Nobel prize in physiology
or medicine for their contribution to the understanding of cell cycle regulation
(1).