Celbiologie en Immunologie. Deeltoets 1
1. De student kan uitleggen hoe cellen zijn opgebouwd, hoe de celcyclus verloopt en hoe die
gecontroleerd wordt, uitleggen wat apoptose is en hoe dat wordt gereguleerd en
voorbeelden geven van cellulaire communicatie en deze uitleggen.
2. De student heeft inzicht in de ontwikkeling en het functioneren van de immuuncellen
betrokken bij de "innate immunity" en "adaptive immunity".
HC 1: Cell 1 Chapter 18
CELL-CYCLE CONTROL SYSTEM
The eukaryotic cell cycle usually occurs in four phases.
The cell grows continuously during interphase, which
consists of three phases: G1, S and G2. During M phase,
the nucleus divides in a process called mitosis; then the
cytoplasm divides, in a process called cytokinesis.
IPMAT; interfase, (prometafase), profase, metafase, anafase, telofase
The cell-cycle control system ensures that key processes
in the cycle occurs in the proper sequence. This is
achieved by employing so called checkpoints to pause
the cycle at certain transition points.
Cells may even enter G0, a specialized resting state (liver)
The cell-cycle control system depends on cyclically activated protein kinases called Cdks (cyclin-
dependent protein kinases). Cdk must bind a regulatory protein called a cyclin and become
phosphorylated before it can become enzymatically active. Therefore the activity depends on cyclin
concentration and (de)phosphorylation (phosphatases and kinases). When activated, Cdks
phosphorylate key proteins in the cell.
Different cyclin–Cdk complexes trigger different steps of the cell cycle: G1-Cdk drives the cell through
G1; G1/S-Cdk and S-Cdk drive it into S phase; and M-Cdk drives it into mitosis.
The accumulation of cyclins helps regulate the activity
of Cdks. Although the enzymatic activity of each type
of cyclin-Cdk complex rises and falls during the course
of the cell cycle, the concentration of the Cdk
component does not (not shown)
The control system also uses protein complexes, such
as APC/C (anaphase-promoting complex or glycosome),
to trigger the destruction of specific cell-cycle
regulators at particular stages of the cycle (it marks cyclins with ubiquitin proteasomes
The cell-cycle control system can halt the cycle at specific transition points to ensure that
intracellular and extracellular conditions are favourable and that each step is completed before the
next is started. Some of these control mechanisms rely on Cdk inhibitors that block the activity of one
or more cyclin–Cdk complexes.
The cell-cycle control system uses various mechanisms to
pause the cycle at specific transition points. To accomplish
these feats, the control system uses a combination of the
mechanisms we have described. At the G1-to-S transition, it
uses Cdk inhibitors to keep cells from entering S phase and
replicating their DNA (see Figure 18−11). At the G2-to-M
transition, it suppresses the activation of M-Cdk by inhibiting
the phosphatase required to activate the Cdk (see Figure
18−10). And it can delay the exit from mitosis by inhibiting the
activation of APC/C, thus preventing the degradation of
M cyclin (see Figure 18−9).
S-Cdk initiates DNA replication during S phase and helps
ensure that the genome is copied only once. The cell-cycle
control system can delay cell-cycle progression during G1 or S
phase to prevent cells from replicating damaged DNA. It can
also delay the start of M phase to ensure that DNA replication
Retinoblastoma protein (Rb) binds to particular transcription regulators and prevents them from
turning on the genes required for cell proliferation. Mitogens binding to cell-surface receptors
activate intracellular signaling pathways that lead to the formation and activation of G1-Cdk and
G1/S-Cdk complexes. These complexes phosphorylate, and thereby inactivate, the Rb protein,
releasing the transcription regulators needed to activate the transcription of genes required for entry
into S phase.
DNA damage can arrest the cell cycle in G1. When DNA is damaged, specific protein kinases respond
by both activating the p53 protein and halting its otherwise rapid degradation. Activated p53 protein
thus accumulates and stimulates the transcription of the gene that encodes the Cdk inhibitor protein
p21. The p21 protein binds to G1/S-Cdk and S-Cdk and inactivates them, so that the cell cycle arrests
in G1.If the damage is beyond repair, P53 can induce apoptosis. (damaged P53 high mutation rate
tendency to be cancerous)
Many cells in the human body stop permanently stop dividing when they differentiate, terminally
differentiated cells, such as nerve or muscle cells
The initiation of DNA replication takes place in
two steps. During G1, Cdc6 binds to the ORC
(origin recognition complex), and together these
proteins load a pair of DNA helicases on the DNA
to form the prereplicative complex. At the start of
S phase, S-Cdk triggers the firing of this loaded
replication origin by guiding the assembly of the
DNA polymerase (green) and other proteins (not
shown) that initiate DNA synthesis at the
replication fork (discussed in Chapter 6). S-Cdk also
blocks re-replication by phosphorylating Cdc6 (not
shown) and the ORC. This phosphorylation keeps
these proteins inactive and prevents the
reassembly of the prereplicative complex until the
Cdks are turned off in the next G1.
Centrosomes duplicate during S phase and separate during G2. Some of the microtubules that grow
out of the duplicated centrosomes interact to form the mitotic spindle.
If DNA replication stalls, the appearance of single-stranded DNA at the replication fork triggers a DNA
damage response. Part of this response includes the inhibition of the phosphatase Cdc25, which
prevents the removal of the inhibitory phosphates from M-Cdk. As a result, M-Cdk remains inactive
and M phase is delayed until DNA replication is complete and any DNA damage is repaired.
Activated M-Cdk indirectly activates more M-Cdk, creating a
positive feedback loop. Once activated, M-Cdk phosphorylates,
and thereby activates, more Cdk-activating phosphatase (Cdc25).
This phosphatase can now activate more M-Cdk by removing the
inhibitory phosphate groups from the Cdk subunit.
Cohesins and condensins help to configure duplicated chromosomes for segregation. (A) Cohesins
tie together the two adjacent sister chromatids in each duplicated chromosome. They are thought to
form large protein rings that surround the sister chromatids, preventing them from coming apart,
until the rings are broken late in mitosis. (B) Condensins help coil each sister chromatid (in other
words, each DNA double helix) into a smaller, more compact structure that can be more easily
segregated during mitosis. These cartoons illustrate one way that condensins might package
chromatids; the exact mechanism is not known.
Celbiologie en Immunologie. Deeltoets 1