%0 Journal Article
%T PTIP associates with Artemis to dictate DNA repair pathway choice.
%A Wang J
%A Aroumougame A
%A Lobrich M
%A Li Y
%A Chen D
%A Chen J
%A Gong Z
%J Genes Dev
%V 28
%N 24
%D Dec 2014 15
%M 25512557
%F 12.89
%R 10.1101/gad.252478.114
%X PARP inhibitors (PARPis) are being used in patients with BRCA1/2 mutations. However, doubly deficient BRCA1(-/-)53BP1(-/-) cells or tumors become resistant to PARPis. Since 53BP1 or its known downstream effectors, PTIP and RIF1 (RAP1-interacting factor 1 homolog), lack enzymatic activities directly implicated in DNA repair, we decided to further explore the 53BP1-dependent pathway. In this study, we uncovered a nuclease, Artemis, as a PTIP-binding protein. Loss of Artemis restores PARPi resistance in BRCA1-deficient cells. Collectively, our data demonstrate that Artemis is the major downstream effector of the 53BP1 pathway, which prevents end resection and promotes nonhomologous end-joining and therefore directly competes with the homologous recombination repair pathway.