The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer.

Loss of the RAD9A-HUS1-RAD1 (9-1-1) complex in BRCA2-deficient cancer cells causes PRIMPOL-dependent ssDNA gap accumulation, pathological expansion, and increased DNA damage.

• Why it matters: ssDNA gaps are a hallmark of BRCA2-deficient cells, but the mechanisms that protect these lesions and prevent genomic instability were unclear.
• What they did: A genome-wide CRISPR screen in isogenic BRCA2-proficient and BRCA2-deficient cancer cells identified 9-1-1 as essential for survival via an ATR-independent mechanism; 9-1-1 loss increased PRIMPOL-dependent gaps and EXO1-mediated degradation, which was rescued by EXO1 depletion.
• The result: The 9-1-1 complex is linked to POLθ-dependent gap filling and protects gap stability, implying a therapeutic vulnerability in BRCA2-deficient cancers.