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← Theoretical B

Q3 — BRCA1/53BP1 and DNA Double-Strand Break Repair Pathway Choice

Theoretical B Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license
DNA Repair & Recombination

DNA double-strand breaks (DSBs) occur when both strands of the DNA molecule are broken, leading to cell death if not properly repaired. DSBs occur frequently and are primarily repaired through homologous recombination (HR) or non-homologous end-joining (NHEJ). As shown in Figure 1, the BRCA1 protein, when activated by DSBs, inhibits the 53BP1 protein, promoting the HR pathway. Alternatively, 53BP1 can be recruited to DSB sites, where it promotes the NHEJ pathway. Activation of either HR or NHEJ can be sufficient for cell survival. Figure 2 shows the level of BRCA1 protein and cell cycle profile of normal cells. 53BP1-deficient cells have similar BRCA1 protein and cell cycle profile as normal cells. 53BP1 protein level remains relatively same throughout the cell cycle in both normal and BRCA1-deficient cells. BRCA1 is required for the activation of the HR pathway regardless of the presence of 53BP1.

Diagram of a chromosome experiencing a double-strand break, branching into a BRCA1-mediated HR pathway (inhibiting 53BP1) and a 53BP1-mediated NHEJ pathway, both leading to DSB repair and cell survival. Figure 1. DSB repair pathways in normal cells. The red arrow indicates inhibition.

Two graphs: BRCA1 protein level (%) over 20 hours rising and falling in a curve, and a stacked bar chart of the proportion of cells in G1/S/G2-M phases over the same time course. Figure 2. Normal cells were sampled over 20 hours and BRCA1 protein concentration relative to the maximum and the proportions of cells in various stages of cell cycle are analyzed. Y1 = BRCA1 protein (%). Y2 = % of Cells. X = Hours.

On your answer sheet, indicate “T” for true statements and “F” for false ones.

A. The DSB repair pathway choice correlates with cell cycle status.
B. BRCA1-deficient cancer cells exhibit an increased reliance on the NHEJ pathway for DNA repair.
C. In normal cells, the HR pathway is more active in the G1 phase compared to the G2 phase.
D. Inhibitors of the transition from the G1 to the S phase will be more detrimental to 53BP1-deficient cells compared to BRCA1-deficient cells.
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Question reproduced from IBO 2024, Theoretical Exam Part B, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF