BRCA1 and BRCA2 proteins are essential for homologous recombination (HR) repair of double-strand breaks. BRCA2 functions by loading which protein onto single-stranded DNA coated with RPA at DSB resection tails, initiating strand invasion of the sister chromatid?

• A Ku70/Ku80 heterodimer
• B PCNA sliding clamp
• C RAD51 recombinase ✓
• D Fanconi anemia complementation group A (FANCA)

Explanation

Following DSB resection, single-stranded DNA is coated by RPA (replication protein A). BRCA2 directly binds RAD51 via its BRC repeats (and the C-terminal domain) and displaces RPA, loading RAD51 onto the ssDNA to form a nucleoprotein filament. This RAD51 filament performs strand invasion into the homologous sequence on the sister chromatid, initiating HR. BRCA1 facilitates upstream resection and also interacts with PALB2 which bridges BRCA1 and BRCA2. Ku70/Ku80 mediates the competing NHEJ pathway. BRCA1/2 loss causes reliance on error-prone NHEJ and PARP-dependent single-strand break repair, which is why PARP inhibitors (olaparib) are synthetically lethal in BRCA-mutant cancers.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.