i want 30 mutiple choice questions with their model answer below each question that covers all the different aspects of all of the following information :
The Essence of Molecular Biology
In molecular biology, we connect the genotype of individuals, that is, the
content of their DNA, to their phenotype, which is the expression of that
genotype in their appearance and the way their bodies function. The
relationship between genotype and phenotype is complex, and involves
the dynamic interaction of genes, and the proteins they encode, with
myriad environmental stimuli.The Essence of Molecular Biology
The genetic information on which the phenotype is built is contained in
every cell in the form of DNA. Replication is the process by which DNA is
duplicated. This process is undertaken prior to cell division to ensure that
all daughter cells contain the same genetic information as the parent cell.
The information in DNA is transmitted to RNA via a process called
transcription . RNA synthesizes protein through the process of translation,
which largely controls the appearance and function (i.e., the phenotype)
of cells and organisms.Lecture’s Objectives
1. Define cell cycle.
2. List the phases of the cell cycle.
3. Describe the molecular events taking
place during various phases of a cell
cycle.
4. Explain how the cell cycle is
regulated.
5. Correlate the disturbances in cell
cycle regulation with cancer.
6. Define apoptosis.
7. Explain the significance of apoptosis.
8. Describe the pathways involved of
the process of apoptosis.What is the cell cycle?
Definition
A cell cycle is a series of events that takes place in a cell as it grows and divides.
A cell spends most of its time in what is called interphase, and during this time it
grows, replicates its chromosomes, and prepares for cell division.
The cell then leaves interphase, undergoes mitosis, and completes its division.
The resulting cells, known as daughter cells, each enter their own interphase and
begin a new round of the cell cycle.Phases of the cell cycle
• Successive phases of progression of a cell through its cycle of
replication are defined with reference to DNA synthesis and cellular
division.
1- DNA synthesis occurs only during a limited period of the cell cycle,
which is the S- phase .2- The cell-division stage or M phase comprising nuclear division (mitosis)
and cytoplasmic division (cytokinesis).
3- First gap phase (G 1 ) which occurs following the M phase.
4- Second gap phase (G 2 ) which separates the S-phase from the M phase.
• Although initially regarded as periods of inactivity, it is now recognized that
these gap phases represent periods when critical processes occur,
preparing the cells for DNA synthesis and mitosis.Phases of the cell cycle• After cell division (mitosis), individual daughter cells may re-enter G 1 to
undergo further division if appropriate stimuli are present.
• Alternatively, they may leave the cycle and become quiescent or resting
cells — a state often labelled as G 0 (resting phase).
• Entry to G 0 may be associated with a process of terminal
differentiation , with loss of potential for further division and death at the
end of the lifetime of the cell; this occurs in permanent cells, such as
neurons. Other quiescent cells retain some ability to proliferate by reentering G 1 if appropriate stimuli are present.Schematic of the cell cycle. Outer ring: I = Interphase, M
= Mitosis; inner ring: M = Mitosis, G1 = Gap 1, G2 = Gap
2, S = Synthesis; not in ring: G0 = Gap 0/RestingDuration of the cell cycle
• In mammals, different cell types divide at very different rates, with the cell cycle ranging from
as little as 8 hours, in the case of gut epithelial cells, to 100 days or more, exemplified by
hepatocytes in the normal adult liver.
• However, the duration of the individual phases of the cycle is constant and independent of
the rate of cell division.
• The principal difference between rapidly dividing cells and those that divide slowly is the
time spent temporarily in G 0 between divisions; some cells remain in the G 0 phase for days
or even years between divisions, whilst others rapidly reenter G 1 after mitosis.Molecular events in the cell cycle
• Cell division is a highly complex process and cells possess a molecular
machinery to ensure its successful completion.
• A number of internal checkpoints exist to ensure that one phase is complete
before the next commences. This is vital to ensure that DNA replication has
been performed accurately and that cells do not divide before DNA replication
is complete.
• The various proteins and enzymes that carry out DNA replication, mitotic
spindle formation are typically only present and active during the appropriate
phases of the cycle.Cell Cycle Checkpoints• The cell cycle is regulated by the activity of a family of proteins called cyclindependent kinases (CDKs).
• CDKs activate their target proteins by phosphorylation.
• The activity of CDKs is regulated by a second family of proteins,
the cyclins .
• Transitions from one phase of the cycle to the next are initiated by rises in
the levels of specific cyclins.
Regulation of the Cell Cycle• Cyclin D triggers the transition from G0 to G1 at the initiation of the cell cycle.
This occurs when stimulated by growth factors.
• Errors during DNA replication rises in the levels of certain proteins called
the CDK inhibitors (CDKIs) which prevent CDKs from triggering the next
phase of cell division until the issue is resolved.
• If the cells fail to correct and repair these errors, they will typically initiate
apoptosis rather than permit the generation of improper daughter cells.Disturbances in the cell cycle is associated
with cancer
• Damage to the genes that encode proteins involved in the regulation of cellcycle progression is seen in many cancers.
• In normal cells, hundreds of genes control the process of cell division. Normal
growth requires a balance between the activity of those genes that promote cell
proliferation and those that suppress it. It also relies on the activities of genes
that signal when damaged cells should undergo apoptosis.• Cells become cancerous after mutations accumulate in the various genes
that control cell proliferation.
• According to research findings from the Cancer Genome Project, most
cancer cells possess 60 or more mutations.
• Different kinds of cancers have different mutational signatures. However,
scientific comparison of multiple tumor types has revealed that certain genes
are mutated in cancer cells more often than others.• Growth-promoting genes, such as the gene for the signaling protein Ras, are
among those most commonly mutated in cancer cells, becoming super-active
and producing cells that are too strongly stimulated by growth receptors.
• Other cancer-related mutations inactivate the genes that suppress cell
proliferation or those that signal the need for apoptosis. These genes, known
as tumor suppressor genes, normally function like brakes on proliferation, and
both copies within a cell must be mutated in order for uncontrolled division to
occur. For example, many cancer cells carry two mutant copies of the gene that
codes for p53, the “guardian of the genome,” a multifunctional protein that
normally senses DNA damage and acts as a transcription factor for checkpoint
control genes.• Many of the drugs used in the treatment of cancer affect particular stages
within the cell cycle.
• These drugs inhibit the rapid division of cancer cells, but since they are
administered systemically there is often inhibition of other rapidly dividing cells,
such as the cells of the bone marrow and lymphoid tissues.
• Thus anemia, a bleeding tendency and suppression of immunity may be
clinically important side effects of cancer chemotherapy.
Regulatory proteins of the cell cycle are
targets for anticancer drugsTherapeutic interruption of the cell
cycleApoptosis
Definition
Physiological cell death.
Apoptosis is a physiological cellular process in which a defined
and programmed sequence of intracellular events leads to the
removal of a cell without the release of products harmful to
surrounding cells.Significance of Apoptosis
• The coexistence of apoptosis alongside mitosis within a cell population
ensures a continuous renewal of cells, rendering a tissue more adaptable
to environmental demands than one in which the cell population is static.
• It is an energy-dependent, biochemically specific mode of cell death
characterized by the enzymatic digestion of nuclear and cytoplasmic
contents, and the phagocytosis of the resultant breakdown products whilst
still retained within the cell membrane.• p53 is a multifunctional protein which induces cell cycle arrest and
initiates DNA damage repair. However, if this is unsuccessful, p53 can
induce apoptosis via activation of proapoptotic members• The nucleus shrinks (pyknosis) and fragments (karyorrhexis). The cell
shrinks, retaining an intact plasma membrane, but alteration of this
membrane rapidly induces phagocytosis.
• Dead cells not phagocytosed fragment into smaller membranebound apoptotic bodies.
• There is no inflammatory reaction to apoptotic cells, probably because the
cell membrane is intact