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F1000Prime Recommended Article: Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Total Score (stars): 3

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By Chiang TW, de Krijger I, Martin AG, Sczaniecka-Clift M
| f1000.com
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome CRISPR-Cas9 synthetic-viability/resistance screens in BRCA1-deficient breast cancer cells treated with PARP inhibitors. We identified two previously uncharacterized proteins, C20orf196 and FAM35A, whose inactivation confers strong PARP-inhibitor resistance.
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