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Summary Essential Cell Biology CH18
- Instelling
- Universiteit Utrecht (UU)
The key concepts of this chapter that are needed for this course are summarized.
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The cell division cycle
Cell cycle = the cycle of Studies of yeast can lead
duplication and division insights into biology of
↳ Essential mechanism by which all living things reproduce
human cancers, because the
cell-cycle control is similar in
all eukaryotes. The basic
organisation of the cycle is
essentially the same in all
eukaryotic cells, and they all
appear to use similar
machinery and control
mechanisms to drive and
regulate cell-cycle events.
OVERVIEW OF THE CELL CYCLE
Interphase = the period between one M phase and THE CELL-CYCLE CONTROL SYSTEM
the next (encompasses the remaining three phases
of the cell cycle) The cell-cycle control system depends on cyclically
activated protein kinases called Cdks. The cell-cycle
control system uses the mechanism of
The eukaryotic cell cycle usually includes four phases. phosphorylation (carried out by kinases) followed by
M phase: consist of mitosis dephosphorylation (preformed by phosphatases) to
(when the nucleus divides) switch the activity of a protein and protein
and cytokinesis (when the complexes on and off.
cell splits itself in two).
G phase: cell continues to
grow, and monitors both
internal state and external
environment, which ensures
that the conditions are
suitable for reproduction.
Decides whether to proceed The protein kinases are activated only at
to the next phase or to appropriate times in the cycle, after which they are
pause. quickly inactivated. Thus the activity of each kinases
S phase: the cell replicates its DNA (S = synthesis) rises and falls in a cyclical fashion.
G phase: same as G phase.
2
Cyclins, another set of proteins in the control
If the interphase (S, G and G ) lasted only long
2
system, have no enzymatic activity themselves, but
enough for DNA replication, the cell would not have they must bind to the cell-cycle kinases (cyclin-
time to double its mass before it divided and would can becomeprotein
dependent kinase = Cdk), before the kinases
enzymatically active.
constantly shrink with each cell division. In an early Cyclins concentrations vary in a cyclical fashion
frog embryo the first cell divisions after during the cell cycle, which help drive the cyclic
fertilisation serve to subdivide the giant egg cell assembly and activation of cyclin-Cdk complexes
into many smaller cells as quickly as possible. In such (these help trigger various cell-cycle events).
embryonic cell cycles, the G and G phases are2
drastically shortened, and the cells do not grow
before they divide.
A cell-cycle control system, a complex network of
regulatory proteins, triggers the major processes
of the cell cycle. This system make sure that
eukaryotic cells replicate the DNA and organelles,
and divide in an orderly manner. The progression
through the cell, continuing with the next phase, is Different cyclin-Cdk complexes trigger different steps
regulated at three main transition points. in the cell cycle. Each of the cyclin-Cdk complexes
1. G to S phase: is the environment favourable for
9
phosphorylates a different set of target proteins in
prolifation the cell. M cyclin, which triggers G to enter into M
2
2. G to M phase: is the DNA undamaged and fully
2
phase forms an activated complex with Cdk called M-
replicated Cdk. S cyclins and G /S cyclins bind to Cdk late in G to
3. Mitosis: are the chromosomes properly attached form S-Cdk and G /S-Cdk, which help launch the S
to the mitotic spindle, before the spindle pulls them phase. G cyclins bind to Cdk to form G -Cdk, which help
apart and segregates them into daughter cells. drive the cell through G towards S phase.
, cyclin-Cdk complexes to further regulation their
activity if more time is needed in a particular phase.
Extracts prepared from cells is different phases of The cell-cycle control system
the cell-cycle have been used to identify components can pause the cycle in
of the cell-cycle control system. An extract can be various ways. The cell-cycle
made from dividing cells (frog eggs) and it will control system can
represent the cell cycle stage at the time the transiently delay progress
extract was made. The extract can the be injected through the cycle at various
into other cells and the effect on cell behaviour can transition points and uses a
be observed to determine the function of the cell- combination of the
cycle components present. mechanisms for pausing or
continuing.
- G to S transition: uses Cdk
:
inhibitors to prevent cells
form entering the S phase
and replicating their DNA.
- G to M transition: inhibits
phosphatase required to
activate M-Cdk.
The researchers studied which mutant yeasts got - Exit form mitosis: delays by inhibiting activation of
stuck or didn't behave right at the certain points in APC/C to prevent M cyclin degradation and exit from
the cell cycle to determine which genes (and thus mitosis.
proteins) were responsible for parts of the cell G PHASE
cycle. Cdk and cyclin genes were one group that they G -to-S transition in yeast is sometimes called start,
1
found, and could soon identify in human cells to. because passing it represents a commitment to
Cyclin concentrations are regulated by transcription complete a full cell cycle.
and by proteolysis. Concentration of each cyclin Cdks are stably inactivated in G . Cyclin-Cdk
type rises gradually due to continued transcription complexes (S-Cdks and M-Cdks which must be disabled
of cyclin genes and synthesis of cyclin proteins. The before the end of the phase) are inhibited as cells
abrupt drop in cyclin concentration is due to enter G , by eliminating all the existing cyclins, by
destruction id the cyclin proteins (M and S cyclins are blocking the synthesis if new ones, or by deploying
marked with ubiquitin by anaphase-promoting Cdk inhibitor proteins to stop the activity of the
complex or cyclosome (APC/C), which triggers remaining cyclin-Cdk complexes.
degradation by proteasomes). The destruction of
the cyclins can also help propel the cell cycle Mitogens promote the production of the cyclins that
forward, for example M cyclin degradation helps stimulate cell division. Mammalian cells will multiply
move the cell out of mitosis. only if they are stimulated to do so by extracellular
signals, called mitogens. When cells are deprived of
mitogens long enough, the cell (arrest in G ) will
withdraw from the cell cycle and enter a non
proliferating state.
Mitogens act by switching on cell signalling pathways
that stimulate the synthesis of G cyclins, G /S cyclins
and other proteins involved with DNA synthesis and
chromosome duplication.
Retinoblastoma (Rb) protein is a negative control
The activity of cyclin-Cdk complexes depend on that block progression from the G to S phase. Rb
phosphorylation and dephosphorylation. The cyclin- binds to transcription regulators and prevents them
Cdk complexes contain inhibitory phosphates, and to from turning on the genes required for proliferation.
become active, the Cdk must be dephosphorylated Mitogens release the Rb brake by triggering the
with specific protein phosphatases. activation of G -Cdk and G /S-Cdks that
Cdk inhibitors can help regulate progression through phosphorylate the Rb protein, altering its
the cell cycle, by blocking the Cdk activity. Cdk conformation so it releases its transcription
inhibitors may block the assembly or action of some factors which turn on the genes necessary for
proliferation.
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