Checkpoints

and cancer

Essam Munir ‫عصام منير عبد االمير‬

Group : B (B4)
 Checkpoints and cancer
1- Understand how the eukaryotic cell cycle is controlled, and
why this is important.

Controlling of the cell cycle occurs due to specific signaling

molecules In the cytoplasm and all this occur in series of
checkpoints, each checkpoint determines if the cell is ready to
continue the cycle .The importance of understanding how the
cell cycle is regulated can be observed when we study cancer,
because when we know how the normal cell cycle is done, we
can easily distinguish the timing and rate of cell division is
important for normal growth, healing ( repair ), and for
development, when we have an idea about the cell cycle of each
type of cells, then we will if there's something wrong with its
cycle and that's may indicate cancer and how these cells can
escape from the usual control.

2- What types of enzymes control the transition between one

phase of the eukaryotic cell cycle and the next? How do they
work?

The molecules that are involved in this regulation are: cyclin

and cyclin dependent kinase(CDK) which regulate the activities
of multiple proteins involved in DNA replication and mitosis by
phosphorylating them at specific regulatory sites, activating
some and inhibiting others to coordinate their activities. Each
CDK can associate with different cyclins, and the associated
cyclin determines which proteins are phosphorylated by a
particular cyclin-CDK complex.
3- Discuss the features of the control mechanism regulating
entry into the M-phase of the cell cycle?

the onset of M phase is subject to a number of controls. The

cell mass increases and progress through the cell cycle. Each
cell must attain a critical mass and that determines the overall
periodicity between cell divisions, in other cells ( embryonic
cells ) this period is determined by a timer . a further control,
operative in somatic cells, couples M phase onset with
completion of S phase. This link ensures that M phase is delayed
if chromosomes are damaged or not fully replicated .
4- What role is played by the retinoblastoma and p53 tumor
suppressor gene in controlling the onset of cancer ?

p53, contributes to arrest cells with damaged DNA in G1

and G2. Under some circumstances, such as when DNA damage
is extensive, p53 also activates expression of genes that lead to
apoptosis to prevent the accumulation of multiple mutations that
might convert a normal cell into a cancer cell. The dual role of
p53 in both cell-cycle arrest and the induction of apoptosis may
account for the observation that nearly all cancer cells have
mutations in both alleles of the p53 gene or in the pathways
that stabilize p53 in response to DNA damage. Rb is a growth-
suppressing protein whose activity is controlled by whether or
not it is phosphorylated.When Rb is in the dephosphorylated
form, during the G0 phase and early in the G1 phase, it is active.
Rb exerts its growth-suppressing effects by binding to many
cellular proteins, including the transcription factors of the E2F
family .E2F transcription factors regulate the expression of
numerous genes that are expressed during G1, or at the
transition from the G1 to the S phase, to initiate DNA
replication.

Rb that is bound to an E2F transcription factor inhibits the

transcription factor's activity. Following phosphorylation by
cyclin/CDK complexes, Rb dissociates from E2F, allowing the
transcription factor to bind DNA sequences and activate the
expression of genes necessary for the cell to enter the S phase.
Cyclin D1/CDK4 complexes phosphorylation of Rb during the
middle of the G1 phase. They allow for subsequent
phosphorylation of Rb by additional cyclin/CDK complexes that
act later in the cell cycle. If a mutation occurs in the Rb, then the
protein will lose its function and cancer may develop

5- Understand how signals external to the cell and even external

to the organism can lead to cell division.

The extracellular growth factors that stimulate cell growth

bind to receptors on the cell surface and activate intracellular
signaling pathways. These pathways stimulate the
accumulation of proteins and other macromolecules, and they
do so by both increasing their rate of synthesis and decreasing
their rate of degradation . Some extracellular signal proteins,
including PDGF, can act as both growth factors and mitogens,
stimulating both cell growth and cell-cycle progression. This
functional overlap is achieved in part by overlaps in the
intracellular signaling pathways that control these two
processes. Cell growth and division, however, can be controlled
by separate extracellular signal proteins in some cell types.
Such independent control may be particularly important during
embryonic development, when dramatic changes in the size of
certain cell types can occur. Even in adult animals, however,
growth factors can stimulate cell growth without affecting cell
division. The size of a sympathetic neuron, for example, which
has permanently withdrawn from the cell cycle, depends on the
amount of nerve growth factor (NGF) secreted by the target
cells it innervates. The greater the amount of NGF the neuron
has access to, the larger it becomes. It remains a mystery,
however, how different cell types in the same animal grow to
be so different in size

6- what is cancer and how does it relate to the eukaryotic cell

cycle.
Cancer is an abnormal condition which occurs due to
failures of the mechanisms that usually control the growth and
proliferation of cells

7- Understand the different stages of the eukaryotic cell cycle,

and what happens during each one.

G1 phase growth and synthesis. Gap phase 1 begins at the

completion of mitosis and cytokinesis and lasts until the
beginning of S phase. This phase is generally the longest of the
four cell cycle phases and is quite variable in length. During this
phase, the cell chooses either to replicate its deoxyribonucleic
acid (DNA) or to exit the cell cycle and enter a quiescent state
(the G0 phase).

S phase replication of the chromosomes is restricted to one

specific portion of interphase, called S phase (DNA synthesis
phase), which typically lasts about 6 h. In mammalian cells, the
start of S phase the actual initiation of DNA synthesis takes
place several hours after the cell has committed to carrying out
DNA synthesis. During S phase, each chromosome replicates
exactly once to form a pair of physically linked sister
chromatids. In animal cells, a pair of centrioles is also
duplicated during S phase .

G2 phase - Preparation for division

The portion of interphase that follows S phase is called gap
phase 2. Some cells can exit the cell cycle from G2 phase, just
as they can from G1 phase.
M phase

M phase includes the overlapping processes of mitosis and

cytokinesis. Mitosis is divided into five stages: prophase,
prometaphase, metaphase, anaphase, and telophase.
Cytokinesis usually begins during anaphase and ends at a point
after the completion of mitosis. At the end of cytokinesis, the
parent cell has formed its twG1 phase progeny and the cell is
ready to repeat the cycle.

8- Advantages and disadvantages of checkpoint .

The checkpoint
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. The disadvantage of the checkpoint is slowing the
proliferation process.