Transcriptional profiling of a breast tumor shows high expression of AURKA (Aurora kinase A), which phosphorylates BRCA1 at serine 308. The pathological consequence of AURKA-mediated BRCA1 inactivation specifically impairs which cell cycle checkpoint?

• A G1/S checkpoint via p21 downregulation
• B Spindle assembly checkpoint via BubR1 inhibition
• C S-phase checkpoint via inhibition of origin firing
• D G2/M checkpoint via impaired DNA damage recognition ✓

Explanation

AURKA phosphorylates BRCA1 at serine 308, causing BRCA1 to dissociate from its binding partner BARD1 and abrogating the G2/M DNA damage checkpoint. BRCA1 is essential for recognizing double-strand DNA breaks and activating the G2/M checkpoint by phosphorylating and inactivating CDC25C. This AURKA-BRCA1 interaction explains why some BRCA1-wild type tumors behave similarly to BRCA1-mutant tumors (BRCAness) and may respond to PARP inhibitors.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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