PART 1 : Cancer and Cell Cycle

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Questions and Answers

What is the earliest known documentation of cancer?

Modern pathology textbooks

Edwin Smith Papyrus (~3000 BC) (correct)

Hippocratic Corpus (~400 BC)

Evidence from the 17th century

Which of the following is NOT a recognized cause of cancer?

Chemical carcinogens

High-fiber diets (correct)

Lifestyle factors

Viral infections

What is the median age for cancer diagnosis?

66 years (correct)

40 years

75 years

50 years

Which type of cancer-causing agents includes asbestos and UV radiation?

Physical carcinogens (A) Signup and view all the answers

What triggers the activation of Cdk4-6/Cyclin D complexes during the G1 phase?

Growth factor signaling through pathways like PI3K/Akt/mTOR (B) Signup and view all the answers

Which transcription factor is released when Rb is phosphorylated?

E2F (B) Signup and view all the answers

Which checkpoint verifies that DNA replication is complete and error-free before mitosis?

G2/M checkpoint (B) Signup and view all the answers

Which DNA repair pathway is highly accurate and relies on a complementary DNA strand?

Homologous recombination (HR) (B) Signup and view all the answers

What protein recognizes mismatched bases during DNA replication?

MutS proteins (A) Signup and view all the answers

Why is NHEJ considered error-prone?

It does not restore the original genetic sequence. (C) Signup and view all the answers

What role does BRCA1 play in DNA repair?

It stabilizes the repair complex for homologous recombination. (A) Signup and view all the answers

In which repair pathway are Ku proteins involved?

Non-homologous end joining (NHEJ) (B) Signup and view all the answers

What happens to tumor suppressor genes in cancer?

They are mutated or inactivated. (A) Signup and view all the answers

Which is an example of a tumor suppressor gene?

BRCA1 (A) Signup and view all the answers

What is the inheritance pattern of BRCA1/2 mutations?

Autosomal dominant (B) Signup and view all the answers

Which of the following is a hallmark of cells with defective BRCA1/2?

Genomic instability due to impaired DNA repair (A) Signup and view all the answers

What is the concept of synthetic lethality in cancer treatment?

Exploiting specific vulnerabilities in cancer cells that rely on defective pathways. (D) Signup and view all the answers

How does p53 respond to DNA damage?

By initiating apoptosis or cell cycle arrest. (B) Signup and view all the answers

What is the role of Myc in cancer?

It regulates the cell cycle and is hyper-activated in cancer. (B) Signup and view all the answers

What happens to cells at the metaphase-to-anaphase checkpoint if chromosomes are not properly attached to spindle fibers?

Mad2 inhibits APC/C, halting progression. (A) Signup and view all the answers

Which phase is characterized by DNA synthesis and replication?

S phase (A) Signup and view all the answers

What enzyme complex promotes chromatin condensation in mitosis?

Cdk1/Cyclin B (C) Signup and view all the answers

Which cyclin activates Cdk4/6 in the G1 phase?

Cyclin D (C) Signup and view all the answers

What molecular pathway does Ras activate in response to growth factors?

MAPK pathway (B) Signup and view all the answers

Which type of DNA damage is most effectively repaired by homologous recombination?

Double-strand breaks (C) Signup and view all the answers

What is the definition of cancer?

Uncontrolled growth of cells that form a mass and invade nearby tissues. (A) Signup and view all the answers

What is the purpose of the G1/S checkpoint?

To verify DNA is intact and nutrients are sufficient for replication. (B) Signup and view all the answers

What is the role of Cdk2/Cyclin A in the S phase?

To initiate DNA replication by recruiting helicase. (B) Signup and view all the answers

How does a proto-oncogene contribute to cancer when mutated?

It becomes an oncogene that promotes uncontrolled cell growth. (B) Signup and view all the answers

What is the therapeutic mechanism of PARP inhibitors?

Blocking single-strand break repair, leading to cell death in HR-deficient cells (B) Signup and view all the answers

What is the main role of tumor suppressor genes?

To inhibit uncontrolled cell growth and division. (C) Signup and view all the answers

Which of the following is NOT a phase of the cell cycle?

Apoptosis phase (D) Signup and view all the answers

How does the G1/S checkpoint function?

It verifies the cell has sufficient size, nutrients, and no DNA damage to proceed. (B) Signup and view all the answers

Which molecule initiates DNA replication during the S phase?

Cdk2/Cyclin A (C) Signup and view all the answers

What happens when BRCA1 or BRCA2 is mutated?

DNA repair via homologous recombination becomes defective. (A) Signup and view all the answers

Which of the following defines proto-oncogenes?

Genes that control normal cell growth and division. (B) Signup and view all the answers

What is the function of the APC/C complex during mitosis?

Separation of sister chromatids by triggering securin degradation. (C) Signup and view all the answers

What is the primary cause of genome instability in BRCA-deficient cells?

Impaired DNA repair via homologous recombination (C) Signup and view all the answers

Which repair mechanism is error-prone and can lead to mutations during DNA repair?

Non-homologous end joining (B) Signup and view all the answers

Which repair mechanism is error-free and use a complementary template DNA?

Homologous recombination (A) Signup and view all the answers

Which checkpoint monitors attachment of chromosomes to spindle microtubules?

Metaphase-to-anaphase checkpoint (C) Signup and view all the answers

What happens when the retinoblastoma (Rb) protein is phosphorylated?

It allows progression from G1 to S phase. (B) Signup and view all the answers

Study Notes

Part 1: General Concepts of Cancer

Earliest known documentation of cancer: Edwin Smith Papyrus (~3000 BC)
Definition of cancer: Uncontrolled growth of cells forming a mass and invading nearby tissues.
Non-recognized cause of cancer: High-fiber diets
Median age for cancer diagnosis: 66 years
Cancer-causing agents (examples): asbestos, UV radiation (physical carcinogens)

Part 2: Cell Cycle and Checkpoints

Purpose of G1/S checkpoint: To verify DNA is intact and sufficient nutrients are available for replication.
Triggers for Cdk4-6/Cyclin D complexes (in G1 phase): Growth factor signaling via pathways like PI3K/Akt/mTOR
Transcription factor released when Rb is phosphorylated: E2F

Part 3: DNA Repair Mechanisms

Highly accurate DNA repair pathway: Homologous recombination (HR)
Protein recognizing mismatched bases during replication: MutS proteins
Error-prone DNA repair pathway: Non-homologous end joining (NHEJ)
Role of BRCA1 in DNA repair: Stabilises the repair complex for homologous recombination
DNA repair pathway involving Ku proteins: Non-homologous end joining (NHEJ)

Part 4: Tumor Suppressor Genes and Proto-Oncogenes

Proto-oncogene mutation effect: Becomes an oncogene, promoting uncontrolled cell growth.
Tumor suppressor gene effect in cancer: Mutated or inactivated
Example of a tumor suppressor gene: BRCA1
Inheritance pattern of BRCA1/2 mutations: Autosomal dominant
Hallmark of cells with defective BRCA1/2: Increased genomic instability due to impaired DNA repair

Part 5: Cancer Therapies and Mechanisms

Mechanism of PARP inhibitors: Blocking single-strand break repair, leading to cell death in HR-deficient cells
Concept of synthetic lethality in cancer treatment: Exploiting specific vulnerabilities in cancer cells that rely on defective pathways

Part 6: Miscellaneous

Phase characterized by DNA synthesis and replication: S phase
Enzyme complex promoting chromatin condensation in mitosis: Cdk1/Cyclin B
Cyclin activating Cdk4/6 in G1 phase: Cyclin D
Molecular pathway activated by Ras in response to growth factors: MAPK pathway
DNA damage type most effectively repaired by homologous recombination: Double-strand breaks

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Description

History of cancer, the cell cycle checkpoints, and DNA repair mechanisms.