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These findings have implications for under-standing cancer-associated PARPi resistance and the evolution of antibody CSR in higher vertebrates.ĭNA damage presents a major threat to genome stability, and cells have therefore evolved elegant mechanisms, collectively referred to as the DNA damage response (DDR), to protect their genome integrity ( Jackson and Bartek, 2009). Shieldin functions as a downstream effector of 53BP1-RIF1 in restraining DNA end resec-tion and in sensitizing BRCA1-deficient cells to PARP inhibitors. Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168–53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unpro-tected telomeres.

#Ddr digital picture recovery crack plus

We identified a novel vertebrate-specific protein complex, shieldin, comprising REV7 plus three previously unchar-acterized proteins, RINN1 (CTC-534A2.2), RINN2 (FAM35A), and RINN3 (C20ORF196). Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-spe-cific interaction modules, and implicate previously concealed regulators in this process. By combining proximity labeling with quantitative mass spectrometry, we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1.

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