To understand the molecular mechanism of cell division, we need to know the
life cycle of a cell. It consists of four phases: G1, S,
G2 and M, where "G" stands for
"Gap", "S" represents "Synthesis" and
"M" means "Mitosis". A newly divided cell may either
enter into another round of cell division or remain in the resting state for a
long period. In the latter case, the cell is said to be in the G0
phase. Upon specific stimulation, cells in the G0 phase may
re-enter the G1 phase.
Figure 8-A-1. The cell cycle.
Without counting the G0 phase, a cell cycle takes 12-24 hours for
most mammalian cells, and only 20-30 minutes for E. coli cells.
CDK and cyclins
The progression of cell cycle is catalyzed by cyclin-dependent kinase (CDK)
which, as the name suggests, is activated by a special class of proteins called cyclins.
In mammals, different cyclins are designated as A, B, C, D and so on. In
budding yeast (S. cerevisiae), nine cyclins have been identified: Cln1 to
Cln3 and Clb1 to Clb6.
The proteins of the CDK superfamily in mammals is denoted by Cdk
followed by a number. However, in yeast, they are denoted by Cdc (cell
division control) and a number. Among them, Cdc2 was first identified in
fission yeast ( S. pombe). It is equivalent to Cdc28 in budding
yeast, and to Cdk1 in mammals. Cdk1 is often referred to as Cdc2.
Figure 8-A-2. Structure of the Cyclin
A-Cdk2 complex. PDB ID = 1FIN.
Figure 8-A-3. The cyclin-CDK complexes involved in
each phase of the cell cycle. The red line indicates the timing a
particular complex is involved.
In budding yeast, the cell cycle is initiated by the binding of Cln1 or Cln2
to Cdc28. Then, Clb5 or Clb6 binds to Cdc28, and pushes the cycle
forward. Clb1 and Clb2 are involved in the final phase.
In mammals, the cell cycle is initiated by the binding of Cyclin D (CycD) to
Cdk4 or Cdk6. The final phase is catalyzed by the binding between Cyclin B
(CycB) and Cdk1. The CycB-Cdk1 complex is known as MPF, which
originally stands for maturation promoting factor, but now also stands
for mitosis promoting factor.
Initiation and termination mechanism of the S phase
p53 and cell cycle control
Review Articles:
Lost
in Transcription: p21 Repression, Mechanisms, and Consequences - Cancer
Research, 2005.
Cellular
Checkpoint Mechanisms Monitoring Proper Initiation of DNA Replication -
J. Bio. Chem., 2005.
Living with
or without cyclins and cyclin-dependent kinases - Genes and Development,
2004.
G2
checkpoint abrogators as anticancer drugs - Mol. Cancer Therap., 2004.
Molecular
Interaction Map of the Mammalian Cell Cycle Control and DNA Repair Systems
- MBC Online, 1999.
CDK
inhibitors: positive and negative regulators of G1-phase
progression - Genes and Development, 1999.
Whose
end is destruction: cell division and the anaphase-promoting complex
- Genes and Development, 1999.
Cyclin
E in human cancers - FASEB J., 1999
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