Comprehensive Physiology Wiley Online Library

Principles of Cell Cycle Control

Full Article on Wiley Online Library


The sections in this article are:

1 Mitosis
1.1 Cdc2: The Archetypal Cyclin‐Dependent Kinase
1.2 Regulation of Cdc2
1.3 Substrates of Cdc2
1.4 Induction of Chromatin Condensation
1.5 Controls Operating within M Phase
2 Cyclin‐Dependent Kinases Other Than Cdc2
2.1 G1
2.2 Cell Cycle Commitment
2.3 Mammalian Nonmitotic Cyclins
2.4 Cell Cycle Commitment and Cancer
3 Cdk Inhibitors
4 Linking Cell Cycle Commitment to S‐Phase Entry
5 S Phase and G2
6 Concluding Remarks
Figure 1. Figure 1.

Points of commitment in eukaryotic cell cycle. Schematic representation of cell cycle is shown, with major events S (DNA synthesis), M (mitosis), gap phases (G1, G2), and cell division (CD) indicated. In yeast and mammalian cells commitment to enter S phase occurs during period in late G1 1, while commitment to enter mitosis 2 is indistinguishable from G2/M transition (for discussion see text).

Figure 2. Figure 2.

Activation of Cdc2 at onset of mitosis. Assembly of Cdc2/cyclin B heterodimers promotes phosphorylation and inactivation of Cdc2 subunit (left). Dephosphorylation of Cdc2 by Cdc25 phosphatase(s) at positions T14 and Y15 leads to generation of active MPF heterodimers (right). Signals relating to DNA damage and completeness of replication impact on balance of Wee1 (a Cdc2 inhibitory kinase) and Cdc25 activities to delay entry into M phase. Additional DNA damage signal may influence aspect of Cdc2 activation other than Y15 phosphorylation (see text).

Figure 3. Figure 3.

Two checkpoints that prevent premature mitosis in fission yeast. In cells that require delay of G1 progression (for example, cells that are too small to satisfy the minimum size requirement for S‐phase entry) Rum1 acts both to delay start and to prevent entry into mitosis. In cells that have passed start, Cdc18 acts to prevent premature mitosis as long as DNA replication is in progress.

Figure 4. Figure 4.

A pathway linking start to the initiation of S phase in fission yeast. Conversion of Cdc2 from “prestart” form to a “poststart” form (asterisk) is inhibited by Rum1. Once activated for its start function, Cdc2 activates transcription factors containing Cdc10 protein and accessory subunits; key target for these transcription factors is cdc18 gene, which encodes protein required for initiation of DNA replication (see text).

Figure 1.

Points of commitment in eukaryotic cell cycle. Schematic representation of cell cycle is shown, with major events S (DNA synthesis), M (mitosis), gap phases (G1, G2), and cell division (CD) indicated. In yeast and mammalian cells commitment to enter S phase occurs during period in late G1 1, while commitment to enter mitosis 2 is indistinguishable from G2/M transition (for discussion see text).

Figure 2.

Activation of Cdc2 at onset of mitosis. Assembly of Cdc2/cyclin B heterodimers promotes phosphorylation and inactivation of Cdc2 subunit (left). Dephosphorylation of Cdc2 by Cdc25 phosphatase(s) at positions T14 and Y15 leads to generation of active MPF heterodimers (right). Signals relating to DNA damage and completeness of replication impact on balance of Wee1 (a Cdc2 inhibitory kinase) and Cdc25 activities to delay entry into M phase. Additional DNA damage signal may influence aspect of Cdc2 activation other than Y15 phosphorylation (see text).

Figure 3.

Two checkpoints that prevent premature mitosis in fission yeast. In cells that require delay of G1 progression (for example, cells that are too small to satisfy the minimum size requirement for S‐phase entry) Rum1 acts both to delay start and to prevent entry into mitosis. In cells that have passed start, Cdc18 acts to prevent premature mitosis as long as DNA replication is in progress.

Figure 4.

A pathway linking start to the initiation of S phase in fission yeast. Conversion of Cdc2 from “prestart” form to a “poststart” form (asterisk) is inhibited by Rum1. Once activated for its start function, Cdc2 activates transcription factors containing Cdc10 protein and accessory subunits; key target for these transcription factors is cdc18 gene, which encodes protein required for initiation of DNA replication (see text).

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Chris Norbury. Principles of Cell Cycle Control. Compr Physiol 2011, Supplement 31: Handbook of Physiology, Cell Physiology: 819-842. First published in print 1997. doi: 10.1002/cphy.cp140121