Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 28-year-old woman receives ionizing radiation for
a localized malignancy. Months later she develops a
secondary malignancy caused by mutations in her
hematopoietic progenitors. Which DNA repair defect most
directly explains accumulation of double-strand breaks
after ionizing radiation?
A. Nucleotide excision repair deficiency
B. Mismatch repair deficiency
C. Homologous recombination repair deficiency
D. Base excision repair deficiency
Answer: C. Homologous recombination repair deficiency
,Rationales
• Correct (C): Homologous recombination repairs DNA
double-strand breaks using a sister chromatid template;
defects (e.g., BRCA pathway) cause persistence of double-
strand breaks after ionizing radiation.
• A: Nucleotide excision repair removes bulky helix-
distorting adducts (UV-induced thymine dimers), not
primarily double-strand breaks.
• B: Mismatch repair corrects replication errors (base–base
mismatches, small indels), not double-strand breaks.
• D: Base excision repair fixes single-base lesions and abasic
sites, not double-strand breaks.
Teaching point: Homologous recombination is the principal
high-fidelity repair for double-strand DNA breaks.
2. Chapter Reference – Chapter 1 — The Genome
Stem: A patient has accelerated aging signs and short
telomeres in dividing cells. Which mechanism best explains
how critically short telomeres lead to permanent cell cycle
arrest?
A. Activation of β-catenin signaling
B. DNA damage response with p53/p21 activation
C. Increased telomerase activity causing oncogene
expression
D. Upregulation of cyclin D to drive G1/S transition
,Answer: B. DNA damage response with p53/p21 activation
Rationales
• Correct (B): Critically short telomeres are recognized as
DNA damage, activating ATM/ATR → p53 → p21, leading to
cell cycle arrest (senescence).
• A: β-catenin is Wnt pathway mediator involved in
proliferation, not the direct sensor of telomere shortening.
• C: Increased telomerase opposes telomere shortening; it
does not cause arrest and is not typically the mechanism in
aging.
• D: Upregulation of cyclin D promotes cell cycle
progression, which contradicts arrest from short
telomeres.
Teaching point: Telomere shortening triggers DNA damage
signaling and p53-mediated senescence.
3. Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A neuron accumulates ubiquitinated, misfolded
proteins in cytoplasmic inclusions. Which intracellular
pathway is most likely impaired?
A. Autophagy–lysosomal pathway
B. Endoplasmic reticulum–Golgi transport
C. Mitochondrial electron transport chain
D. Peroxisomal fatty acid oxidation
, Answer: A. Autophagy–lysosomal pathway
Rationales
• Correct (A): Autophagy delivers aggregated proteins and
damaged organelles to lysosomes for degradation;
impairment leads to protein aggregation (seen in
neurodegenerative disease).
• B: ER–Golgi transport misrouting affects
secreted/membrane proteins but not the primary
clearance of cytoplasmic aggregates.
• C: Mitochondrial ETC dysfunction causes energy failure and
ROS, not direct failure to clear protein aggregates.
• D: Peroxisomal oxidation is unrelated to clearance of
cytoplasmic protein aggregates.
Teaching point: Autophagy clears protein aggregates and
damaged organelles via lysosomal degradation.
4. Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A patient with a genetic defect in the ubiquitin-
activating enzyme (E1) shows accumulation of short-lived
regulatory proteins. Which cellular consequence explains
this finding?
A. Decreased proteasomal degradation of ubiquitylated
proteins
B. Increased lysosomal degradation of cytosolic proteins
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 28-year-old woman receives ionizing radiation for
a localized malignancy. Months later she develops a
secondary malignancy caused by mutations in her
hematopoietic progenitors. Which DNA repair defect most
directly explains accumulation of double-strand breaks
after ionizing radiation?
A. Nucleotide excision repair deficiency
B. Mismatch repair deficiency
C. Homologous recombination repair deficiency
D. Base excision repair deficiency
Answer: C. Homologous recombination repair deficiency
,Rationales
• Correct (C): Homologous recombination repairs DNA
double-strand breaks using a sister chromatid template;
defects (e.g., BRCA pathway) cause persistence of double-
strand breaks after ionizing radiation.
• A: Nucleotide excision repair removes bulky helix-
distorting adducts (UV-induced thymine dimers), not
primarily double-strand breaks.
• B: Mismatch repair corrects replication errors (base–base
mismatches, small indels), not double-strand breaks.
• D: Base excision repair fixes single-base lesions and abasic
sites, not double-strand breaks.
Teaching point: Homologous recombination is the principal
high-fidelity repair for double-strand DNA breaks.
2. Chapter Reference – Chapter 1 — The Genome
Stem: A patient has accelerated aging signs and short
telomeres in dividing cells. Which mechanism best explains
how critically short telomeres lead to permanent cell cycle
arrest?
A. Activation of β-catenin signaling
B. DNA damage response with p53/p21 activation
C. Increased telomerase activity causing oncogene
expression
D. Upregulation of cyclin D to drive G1/S transition
,Answer: B. DNA damage response with p53/p21 activation
Rationales
• Correct (B): Critically short telomeres are recognized as
DNA damage, activating ATM/ATR → p53 → p21, leading to
cell cycle arrest (senescence).
• A: β-catenin is Wnt pathway mediator involved in
proliferation, not the direct sensor of telomere shortening.
• C: Increased telomerase opposes telomere shortening; it
does not cause arrest and is not typically the mechanism in
aging.
• D: Upregulation of cyclin D promotes cell cycle
progression, which contradicts arrest from short
telomeres.
Teaching point: Telomere shortening triggers DNA damage
signaling and p53-mediated senescence.
3. Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A neuron accumulates ubiquitinated, misfolded
proteins in cytoplasmic inclusions. Which intracellular
pathway is most likely impaired?
A. Autophagy–lysosomal pathway
B. Endoplasmic reticulum–Golgi transport
C. Mitochondrial electron transport chain
D. Peroxisomal fatty acid oxidation
, Answer: A. Autophagy–lysosomal pathway
Rationales
• Correct (A): Autophagy delivers aggregated proteins and
damaged organelles to lysosomes for degradation;
impairment leads to protein aggregation (seen in
neurodegenerative disease).
• B: ER–Golgi transport misrouting affects
secreted/membrane proteins but not the primary
clearance of cytoplasmic aggregates.
• C: Mitochondrial ETC dysfunction causes energy failure and
ROS, not direct failure to clear protein aggregates.
• D: Peroxisomal oxidation is unrelated to clearance of
cytoplasmic protein aggregates.
Teaching point: Autophagy clears protein aggregates and
damaged organelles via lysosomal degradation.
4. Chapter Reference – Chapter 1 — Cellular Housekeeping
Stem: A patient with a genetic defect in the ubiquitin-
activating enzyme (E1) shows accumulation of short-lived
regulatory proteins. Which cellular consequence explains
this finding?
A. Decreased proteasomal degradation of ubiquitylated
proteins
B. Increased lysosomal degradation of cytosolic proteins
