Cell cycle and disease

Question 1

Which cells never divide after development?

Answer 1

Mature muscle cells (e.g., cardiac muscle) and nerve cells.

Question 2

Name examples of cells arrested in G0 but capable of resuming proliferation.

Answer 2

Skin fibroblasts, smooth muscle cells, endothelial cells (blood vessels), epithelial cells (liver, pancreas, kidney, lung, prostate, breast).

Question 3

Which tissues rely on continuous renewal by stem cells?

Answer 3

Blood cells and intestinal epithelial cells.

Question 4

How many cells are in an adult human, and how many divide daily?

Answer 4

40 trillion cells, with millions dividing daily for growth and repair.

Question 5

What ensures cell cycle exit upon DNA damage or errors?

Answer 5

Surveillance mechanisms.

Question 6

What happens when cell cycle controls fail, and cells cannot exit the cycle?

Answer 6

Cancer develops, with uncontrolled division leading to mutations and genomic instability.

Question 7

What are proto-oncogenes, and what happens when they mutate?

Answer 7

Genes that regulate cell division. When mutated (oncogenes), they mimic a “stuck accelerator,” causing uncontrolled growth and division.

Question 8

What is the role of tumor suppressors like p53?

Answer 8

Ensure cell cycle exit upon DNA damage. Loss of function leads to defective cycle control and cancer.

Question 9

What percentage of solid tumors show aneuploidy?

Answer 9

~70%.

Question 10

How do cancer cells tolerate aneuploidy?

Answer 10

By mutating p53, increasing replication stress tolerance, and relying on spindle assembly checkpoints (SAC).

Question 11

What is the significance of chromosome translocations in cancer?

Answer 11

They can activate oncogenes (e.g., ABL) or disrupt tumor suppressors, driving cancer progression.

Question 12

What is the cause of Chronic Myeloid Leukemia (CML)?

Answer 12

The BCR-ABL oncogene resulting from chromosome 9 and 22 translocation.

Question 13

What does Rb (retinoblastoma protein) do in the cell cycle?

Answer 13

Prevents entry into the cell cycle by regulating the G1-S transition via the E2F pathway.

Question 14

How does Rb inactivation contribute to cancer?

Answer 14

Leads to loss of cell cycle control, genomic instability, and predisposes patients to various cancers.

Question 15

How do cancer cells benefit from chromosomal instability (CIN)?

Answer 15

CIN provides genetic diversity, aiding tumor evolution and metastasis.

Question 16

What is a key therapeutic strategy targeting cancer cell cycle abnormalities?

Answer 16

Exploiting their reliance on replication stress and SAC checkpoints to induce catastrophic DNA damage.

Question 17

What are the consequences of cell cycle failure during chromosome segregation?

Answer 17

Propagation of mutations, genomic instability, and aneuploidy.

Question 18

What is chromothripsis, and how is it related to cancer?

Answer 18

Chromothripsis is extreme chromosome rearrangement that occurs due to erroneous double-strand break (DSB) repair, often contributing to cancer progression.

Question 19

What causes aneuploidy during mitosis?

Answer 19

Aberrant kinetochore-microtubule attachments.
Supernumerary centrosomes.
Problems in chromosome cohesion.
Cytokinesis failure or cell fusion.

Question 20

What role does p53 play in maintaining genomic integrity?

Answer 20

p53 activates a DNA damage response, halting the cell cycle to repair errors or induce apoptosis if errors persist.

Question 21

What is the relationship between trisomy and cancer?

Answer 21

Certain trisomies (e.g., Chr12 in colorectal cancer) can enhance tumorigenicity and provide selective advantages under stress conditions.

Question 22

What is the spindle assembly checkpoint (SAC), and why is it important in cancer cells?

Answer 22

SAC ensures proper chromosome segregation during mitosis. Cancer cells rely heavily on SAC to avoid catastrophic chromosome missegregation despite chromosomal instability.

Question 23

What is the role of the BCR-ABL chimeric protein in leukemia?

Answer 23

It promotes unchecked cell proliferation through RAS-MAPK, AKT, and JAK-STAT signaling pathways, leading to Chronic Myeloid Leukemia (CML).

Question 24

How does imatinib target Chronic Myeloid Leukemia?

Answer 24

By inhibiting the ABL1 tyrosine kinase activity of the BCR-ABL fusion protein.

Question 25

What is the significance of MYC proto-oncogene translocation in cancer?

Answer 25

MYC translocations place the gene under control of strong promoters, leading to overexpression and cancer, particularly in lymphomas.

Question 26

What are the two types of retinoblastoma, and how do they differ?

Answer 26

Sporadic: Unilateral, no increased risk for other cancers.
Familial: Bilateral, high risk for other cancers due to inherited mutations in RB.

Question 27

What is the impact of loss of Rb function on genomic stability?

Answer 27

Leads to chromosomal instability (CIN), defective DNA damage checkpoints, and improper mitotic progression.

Question 28

What are the challenges in targeting Rb-related cancers therapeutically?

Answer 28

The pleiotropic role of Rb in cell cycle regulation makes it difficult to design specific treatments, compounded by genomic heterogeneity in cancers.

Question 29

How do cancer cells exploit replication stress?

Answer 29

They enhance replication stress tolerance and rely on extended mitosis to prevent catastrophic damage from incomplete DNA replication or spindle assembly.

Question 30

What is the role of supernumerary centrosomes in cancer?

Answer 30

They lead to improper chromosome segregation, contributing to aneuploidy and genomic instability.

Question 31

What happens during a chromosome translocation?

Answer 31

Parts of chromosomes are exchanged incorrectly, often resulting in gene fusions (e.g., BCR-ABL) or misregulation of gene expression.

Question 32

What is the connection between double-strand breaks (DSBs) and chromosome translocations?

Answer 32

Improper repair of DSBs can lead to chromosomal translocations and activation of oncogenes.

Question 33

How does the Rb protein regulate the G1-S transition?

Answer 33

By binding and inhibiting E2F transcription factors, preventing expression of genes required for cell cycle progression.

Question 34

Why is genome integrity critical in preventing cancer?

Answer 34

Disrupted genome integrity (via mutations, aneuploidy, or chromosomal alterations) leads to unchecked cell division and cancer development.

Question 35

How does cancer use chromosomal instability (CIN) as an advantage?

Answer 35

CIN increases genetic diversity, aiding tumor evolution and allowing adaptation to therapeutic stress.

Question 36

What are some promising strategies to target cancer’s reliance on CIN?

Answer 36

Promoting extreme chromosomal instability to induce cell death or targeting SAC reliance and replication stress pathways.