Cancer Biology Quiz on Genes

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Questions and Answers

What is the primary role of oncogenes in cellular processes?

To suppress cell growth

To promote apoptosis in damaged cells

To activate growth-promoting pathways (correct)

To repair DNA damage in cells

Which of the following accurately describes mutator genes in relation to cancer?

They inhibit the function of oncogenes.

They are a type of oncogene involved in cell growth.

They only repair mutations in tumor suppressor genes.

They lead to an increased mutation rate in cells. (correct)

How does the P53 gene contribute to the cellular stress response?

By activating growth-promoting oncogenes

By initiating apoptotic signaling in damaged cells (correct)

By promoting the replication of damaged DNA

By suppressing DNA repair mechanisms

What mechanism does a tumor suppressor gene primarily utilize to prevent cancer development?

Inducing apoptosis in damaged cells Signup and view all the answers

What is a key difference between proto-oncogenes and oncogenes?

Proto-oncogenes are mutated into oncogenes that contribute to cancer. Signup and view all the answers

Which cyclin/CDK complex is responsible for the transition to S-phase?

G1/S-Cdk with Cyclin E Signup and view all the answers

How do mutations in CDKs and cyclins contribute to cancer progression?

They allow cells to continue cycling without regulatory checks. Signup and view all the answers

What environmental factor is specifically mentioned as causing DNA damage linked to skin cancers?

UV light Signup and view all the answers

Which is a common mutation seen in skin cancers related to cell cycle regulation?

CDK4 Signup and view all the answers

Which of the following is true regarding the G0 phase of the cell cycle?

Cells in G0 dismantle their cell cycle machinery. Signup and view all the answers

What role do mutator genes play in cancer development?

They increase the occurrence of spontaneous mutations. Signup and view all the answers

What is the consequence of a G0 cell re-entering G1 phase?

It can take several days to re-enter the cell cycle. Signup and view all the answers

Which of the following best describes proto-oncogenes compared to oncogenes?

Proto-oncogenes can be activated to promote unhealthy cell division. Signup and view all the answers

What is the primary function of oncogenes in cancer development?

To promote uncontrolled cell growth and division Signup and view all the answers

How do tumor suppressor genes contribute to cancer prevention?

By inhibiting cell cycle progression Signup and view all the answers

What role does p53 play in cellular stress response?

Regulates the cell cycle and activates DNA repair mechanisms Signup and view all the answers

Which statement correctly differentiates proto-oncogenes and oncogenes?

Proto-oncogenes are normal genes that can become oncogenes when mutated. Signup and view all the answers

What happens if the spindle assembly checkpoint does not function properly?

Cell division will occur without chromosome alignment. Signup and view all the answers

How do mutations in mutator genes influence cancer risk?

They prevent DNA repairs necessary for healthy cell function. Signup and view all the answers

What is the major signaling role of mitogens in cell cycle regulation?

Promote transition from G0 phase to active cell cycle Signup and view all the answers

What key function do cyclins serve in the cell cycle?

Activate cyclin-dependent kinases (CDKs) Signup and view all the answers

What is the consequence of prolonged checkpoint activation during mitosis?

Delay in cell division leading to possible cell death Signup and view all the answers

Which of the following best describes the role of growth factors in cell cycle regulation?

Increase macromolecule synthesis and decrease breakdown Signup and view all the answers

Study Notes

Cell Cycle Regulation

Cell cycle is strictly regulated. Cells divide only when receiving signals.
Signals include: need for more of that cell type, health/fitness of cell and lack of mutations causing cancer.
Checks ensure each phase is completely before proceeding to next. Example: ensures chromosome replication is complete before mitosis.
Cells check for various issues and can arrest the cell cycle if needed.

Checkpoints

G₂ Checkpoint: Checks DNA replication and damage repair.
Checkpoint in mitosis: Checks chromosome attachments to mitotic spindle.
Enter S phase: Checks if the environment is favourable.
Cells regulate protein activity using phosphorylation and dephosphorylation.

Eukaryotic Cell Signals

Mitogens stimulate cell division by overcoming cell cycle brakes, leading to G₀.
Growth factors stimulate growth (increased cell size) by promoting synthesis and inhibiting degradation of macromolecules.
Survival factors suppress apoptosis (programmed cell death).

Growth Factors

Increase protein synthesis.
Decrease degradation of macromolecules.

Checkpoint: Spindle Assembly

Mitosis is not complete until all chromosomes are attached to the mitotic spindle.
Mitotic checkpoint delays until all chromosomes are attached.
Prolonged checkpoint activation = cell death.
Mechanism of many anti-cancer drugs.

Protein Kinases

Most enzyme activity in cells is regulated.
Cells can switch enzyme activity on/off.
Phosphorylation/dephosphorylation is a common mechanism to regulate a protein's activity.
Adding a phosphate group changes a protein's 3D structure and enzyme activity.
Protein kinases add phosphate groups to other enzymes.

Cyclins & Cyclin-Dependent Kinases (CDKs)

CDKs are proteins that regulate the cell cycle.
CDKs are inactive unless bound to a cyclin.
Active CDKs phosphorylate and activate numerous proteins involved in regulating the cell cycle.

Activity of Cyclins

CDKs are present in the cell throughout the cell cycle.
CDKs, on their own, can't regulate the cell cycle.
M-cyclin concentration increases during interphase, and falls during mitosis.
M-cyclin activates M-Cdk, which triggers mitosis.

What Does M-Cdk Do?

M-cyclin and mitotic Cdk form M-Cdk.
M-Cdk phosphorylates and activates key proteins.
- Cause chromosomes to condense
- Break down the nuclear envelope
- Create the mitotic spindle

Other Cyclins

In addition to M-cyclin/Cdk, there are other cyclins/CDKs that regulate the transition to S-phase.
S-cdk activates proteins to recruit DNA polymerase to replication points and trigger DNA replication.

Relationship Between S-cyclin & M-cyclin

S and M cyclins have specific patterns; they rise and fall in concentration during the cell cycle. This regulates when the relevant CDKs are active.

CDKs & Cyclins (General)

CDKs and Cyclins work together to trigger mitosis, control DNA replication, and regulate the cell cycle.

Major Cyclins & CDKs

A table showing the specific cyclins and CDKs that partner in different phases of the cell cycle.

Cell-Cycle Regulation is Complex

Cyclins and CDKs have specific profiles that control progression through the cell cycle.

Cells Can Withdraw from Cell Cycle & Dismantle Regulatory Machinery

G₀ is a quiescent state, where cells are not dividing or preparing for division.
During G₀, the cell cycle machinery is dismantled (cyclins & CDKs disappear).
Cells can remain in G₀ for their entire lifespan. If the cell re-enters the G₁ phase, the process could take several days.

The Cell Can Stop Cycling

The cell will not progress through the cell cycle if problems or non-ideal conditions exist.
- Damaged DNA detected in G₁, S, or G₂.
- Unfavorable extracellular environment.
- Incompletely duplicated DNA.
- Chromosomes with improper attachments to the mitotic spindle.

CDK & Cancer

Mutations in CDKs and cyclins are common in cancer cells and promote cancer development.
These mutations enable cells to progress through the cell cycle without normal checks, increasing the chance of cell division with cancerous mutations.
Common mutations in skin cancers include CDK4 and CDKN2A/CDKN2B (CDK inhibitors).

Advanced Cyclins/CDKs

A summary outlining the role of different checkpoints in the cell cycle.
Various checkpoints monitor different phases of the cell cycle, regulating progression and halting when issues are detected, including DNA damage.

What Causes Mutations that Lead to Cancer?

Spontaneous changes to the genetic code lead to errors (e.g. depurination)
Free radicals
Food components (e.g., colon cancer)
Cigarette smoke (e.g., lung, throat, tongue, palate cancer)
UV light (e.g., skin cancer)

Exposure to UV Light

UV light damages DNA.
Promotes covalent linkages between two adjacent pyrimidines (e.g., thymine dimers).
May cause mispairing during replication, or prevent replication altogether.
Unrepaired pyrimidine dimers lead to DNA mutations, cell death, and skin cancer.

Thymine Dimer Formation & Repair

UV light causes thymine dimers in DNA.
Repair mechanisms fix these damage.

Oncogenes & Tumour Suppressor Genes

In the initiation phase of cancer, mutations occur in proto-oncogenes that normally regulate cell growth.
The mutated gene is now an oncogene.
Oncogenes stimulate cell growth and division more rapidly than usual.
In the second phase, mutations happen in tumour suppressor genes.
Tumour suppressor genes normally stop cell division or induce apoptosis.

3 Classes of Cancer Causing Genes

Oncogenes accelerate cell growth and proliferation.
Tumour suppressor genes act as a brake on cell division.
Mutations accumulate enabling cancer cells to grow and spread uncontrolled.

Proto-Oncogenes & Oncogenes

Proto-oncogenes are normal genes that promote cell division (e.g. protein kinases, growth factors, transcription factors).
A mutant form of a proto-oncogene is an oncogene, which promotes cell division.
Oncogene activation usually requires a single mutation leading to gain-of-function or expression at wrong quantities, times, or cell types leading to uncontrollable cell division & cancer.

Oncogene Activation

Dominant mutation (gain-of-function): a single mutation in a proto-oncogene creates an oncogene, stimulating cell survival and proliferation.
Normal cells have specific proteins for cell division.
Proto-Oncogene: RAS normally toggles between active and inactive states, but mutations make it constantly active, stimulating cell proliferation and thus contributing to cancerous activity.

Proto-Oncogene: RAS

Normal RAS cycles between active (bound to GTP) and inactive (bound to GDP) states.
30% of cancers have a RAS gene mutation that permanently activates RAS, leading to continuous stimulation of cell division.
These mutations prevent GTP hydrolysis and thus prevent the inactivation of RAS protein.

Tumour Suppressor Genes

Tumour suppressor genes normally prevent cells from dividing.
These genes usually include cell cycle checkpoints and apoptotic inducers.
Cancer can result from a loss-of-function mutation in these genes due to uncontrolled cell proliferation.
Usually both copies of a tumour-suppressor gene need to be mutated to lose the function and thus enable cell proliferation and division.

Tumour Suppressor Gene Inactivation

Recessive mutation: two mutations in a tumour suppressor gene lead to unchecked cell growth.
Loss-of-function mutations in both copies of the gene are needed to enable cell survival and proliferation.

Tumor Suppressor Gene: p53

First discovered as the causative mutation in Li-Fraumeni syndrome.
Present in >50% of human cancers.
Called the "Guardian of the Genome."
p53 is expressed when cells are exposed to DNA damaging agents.
It causes the expression of p21, leading to cell cycle arrest or apoptosis.
This gives cells time to repair damaged DNA and reduces accumulation of damaged cells.

p53 Mechanism of Action

Following cellular stress, p53 induces the expression of p21, a CDK inhibitor.
p21 inhibits the activity of G1/S and S-CDKs.
Cells arrest in G₁ and allows time to repair DNA.
In the absence of p53, p21 is not synthesized and cells don't stop when damaged DNA is present, leading to unchecked cell division with damaged DNA.

Cancer Genes (General)

Cancer development results from accumulation of genetic mutations in multiple genes.
These mutations include somatic mutations (not heritable) and acquired mutations (resulting from environmental factors) which cause the cell cycle to malfunction.

Oncology Genetics

Most cancers are sporadic, resulting from the accumulation of mutations in tissue cells over a lifetime.
Some cancers are inherited due to mutations occurring in germline cells, which leads to higher risk of the individual acquiring additional mutations leading to cancer.
Knudson's hypothesis: requires two "hits" — genetic mutations — to lead to certain types of cancer.

Accumulation of Mutations Causes Cancer

Cancers arise from a progressive build-up of mutations in normal cells.
These mutations turn a cell into a malignant one.

Genetics and Cell Processes for Cancer

Hereditary and sporadic cancers result from the interaction of genetic and cellular processes.
These may be from mutations that cause uncontrolled cell division rates, cell division in inappropriate places, or lack of programmed cell death.

Intratumour Heterogeneity

Tumour cells are not all the same.
Clonal expansion and the accumulation of additional mutations leads to a wide range of variants within a single tumour. These mutations lead to the acquisition of new properties that enable the cancer cells to grow and spread.

Overview of Carcinogenesis

Mutagens (chemicals, radiation, viruses) cause DNA damage.
DNA repair mechanisms either successfully repair the damage or fail.
Faulty DNA repair leads to mutations in somatic cells, which may cause the activation of growth-promoting oncogenes and the impaired apoptotic pathways.
Altered gene products (abnormal proteins) contribute to malignant tumour development.

Resources & Animations

Links to helpful videos and animations about the cell cycle.
Many helpful resources, including animations and simulation tools provide good support for learning about the cell cycle and its associated problems.

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Description

Test your knowledge on the roles of oncogenes, mutator genes, and tumor suppressor genes in cancer biology. This quiz covers key concepts such as P53's role in cellular stress response and distinctions between proto-oncogenes and oncogenes. Perfect for students studying cancer genetics.