Loss-of-function mutations in BRCA1 and BRCA2 predispose to breast and ovarian cancer. Both proteins share a common molecular function that explains this predisposition. What is this shared function?

• A Ubiquitin ligase activity targeting cyclin-dependent kinases
• B Transcriptional repression of VEGF and angiogenic genes
• C DNA double-strand break repair via homologous recombination ✓
• D Inhibition of the Ras-MAPK signalling cascade

Explanation

BRCA1 and BRCA2 are tumor suppressor proteins that play critical roles in the homologous recombination (HR) pathway for DNA double-strand break repair. Loss of either protein impairs high-fidelity HR, forcing cells to use error-prone non-homologous end joining, leading to genomic instability and malignant transformation. This is the molecular basis for the dramatically increased lifetime risks of breast and ovarian cancer in germline mutation carriers, and is also therapeutically exploited by PARP inhibitors (synthetic lethality).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.