V7: cell cycle. The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication (replication). In cells without a nucleus (prokaryotes), the cell cycle occurs via a process termed binary fission. - PowerPoint PPT Presentation
1 V7: cell cycle Cellular Programs WS 2010 – lecture 7 www.wikipedia.o rg The cell cycle, or cell- division cycle, is the series of events that takes place in a cell leading to its division and duplication (replication). In cells without a nucleus (prokaryotes), the cell cycle occurs via a process termed binary fission. Each turn of the cell cycle divides the chromosomes in a cell nucleus. In cells with a nucleus (eukaryotes), the cell cycle can be divided in 2 brief periods: interphase—during which the cell grows, accumulating nutrients needed for mitosis and duplicating its DNA—and the mitosis (M) phase, during which the cell splits itself into two distinct cells, often called "daughter cells".
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V7: cell cycle
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
The cell cycle, or cell-division cycle, is the
series of events that takes place in a cell
leading to its division and duplication
(replication).
In cells without a nucleus (prokaryotes),
the cell cycle occurs via a process termed
binary fission.
Each turn of the cell cycle divides the chromosomes in a cell nucleus.
In cells with a nucleus
(eukaryotes), the cell cycle can
be divided in 2 brief periods:
interphase—during which the
cell grows, accumulating
nutrients needed for mitosis and
duplicating its DNA—and
the mitosis (M) phase, during
which the cell splits itself into two
distinct cells, often called
"daughter cells".
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Phases
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
The cell cycle consists of 4 distinct phases:
- G1 phase,
- S phase (synthesis),
- G2 phase (collectively known as interphase)
- and M phase (mitosis).
Activation of each phase is dependent on the
proper progression and completion of the
previous one.
Cells that have temporarily or reversibly stopped
dividing are said to have entered a state of
quiescence called G0 phase.
Schematic of the cell cycle.
Outer ring:
I = Interphase, M = Mitosis;
Inner ring:
M = Mitosis, G1 = Gap 1, G2 =
Gap 2, S = Synthesis.
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Activity during 4 phases
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
M phase itself is composed of 2 tightly coupled processes:
- mitosis, in which the cell's chromosomes are divided between the two daughter
cells, and
- cytokinesis, in which the cell's cytoplasm divides in half forming distinct cells.
Cdk1 modulates the activity of several DNA damage checkpoint proteins
Cellular ProgramsWS 2010 – lecture 7
Enserink and Kolodner Cell
Division 2010 5:11
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Cd1-controlled targets and processes
Cellular ProgramsWS 2010 – lecture 7
Enserink and Kolodner
Cell Division 2010 5:11
Abstract
The cyclin dependent kinase Cdk1 controls the cell cycle, which is best understood in the
model organism S. cerevisiae. Research performed during the past decade has significantly
improved our understanding of the molecular machinery of the cell cycle. Approximately 75
targets of Cdk1 have been identified that control critical cell cycle events, such as DNA
replication and segregation, transcriptional programs and cell morphogenesis.
....
Conclusions
In conclusion, the identification of Cdk1 targets during the past decade has greatly improved
our understanding of the molecular mechanism of the cell cycle. Nonetheless, much work still
needs to be done because many targets remain to be identified, the exact phosphorylation
sites of many known Cdk1 targets have not been mapped and the consequences of these
phosphorylations at the molecular often remain elusive.
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Cell cycle checkpoints
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell
division in eukaryotic cells.
These checkpoints verify whether the processes at each phase of the cell cycle
have been accurately completed before progression into the next phase.
An important function of many checkpoints is to assess DNA damage, which is
detected by sensor mechanisms.
When damage is found, the checkpoint uses a signal mechanism either to stall the
cell cycle until repairs are made or, if repairs cannot be made, to target the cell for
destruction via apoptosis (effector mechanism).
All the checkpoints that assess DNA damage appear to utilize the same sensor-
signal-effector mechanism.
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G1 checkpoint
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
The first checkpoint is located at the end of the cell cycle's G1 phase, just before
entry into S phase, making the key decision of whether the cell should divide, delay
division, or enter a resting stage.
Many cells stop at this stage and enter a resting state called G0.
Liver cells, for example, enter mitosis only around once or twice a year.
The G1 checkpoint is where eukaryotes typically arrest the cell cycle if
environmental conditions make cell division impossible or if the cell passes into G0
for an extended period.
In animal cells, the G1 phase checkpoint is called the restriction point, and in yeast
cells it is called the Start point.
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G2 checkpoint
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
The second checkpoint is located at the end of G2 phase, triggering the start of the
M phase (mitosis). In order for this checkpoint to be passed, the cell has to check a
number of factors to ensure the cell is ready for mitosis.
If this checkpoint is passed, the cell initiates many molecular processes that signal
the beginning of mitosis. The CDKs associated with this checkpoint are activated by
phosphorylation of the CDK by the action of a "Maturation promoting factor" (or
Mitosis Promoting Factor, MPF).
The molecular nature of this checkpoint involves the activating phosphatase Cdc25
which under favourable conditions removes the inhibitory phosphates present within
the MPF complex.
However, DNA is frequently damaged prior to mitosis, and, to prevent transmission
of this damage to daughter cells, the cell cycle is arrested via inactivation of the
Cdc25 phosphatase.
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Metaphase checkpoint
Cellular ProgramsWS 2010 – lecture 7
www.wikipedia.org
The mitotic spindle checkpoint occurs at the point in metaphase where all the chromosomes have/should have aligned at the mitotic plate and be under bipolar tension.
The tension created by this bipolar attachment is what is sensed, which initiates the anaphase entry. This sensing mechanism allows the degradation of cyclin B, which harbours a D-box (destruction box).
Degradation of cyclin B ensures that it no longer inhibits the anaphase-promoting complex, which in turn is now free to break down securin. The latter is a protein whose function is to inhibit separase, the protein composite responsible for the separation of sister chromatids.
Once this inhibitory protein is degraded via ubiquitination and subsequent proteolysis, separase then causes sister chromatid separation. After the cell has split into its two daughter cells, the cell enters G1.
According to the classical model of cell-cycle control ......The first serious blow to this oderly scheme was the discovery that mice that lack CDC2, although infertile, are viable and healthy....Deletion of other CDKs and cyclins in mice led to a ruther revision of the „specialized CDK“ hypothesis for the mammalian cell cycle....Santamaria et al. Recently published the ultimate step in this line of work....
Why were the earlier experiments so misleading?Quite simply, they were not sufficiently rigorous.
Antibody injection and antisense experiments are inherently difficult to control and interpret correctly, and they cannot substitute for ablations that are achieved using gene-targeting.
Although dominant-negative mutants give clear results, they can be problematic if several kinases share the same activating partners.
