| Title | PTIP associates with Artemis to dictate DNA repair pathway choice |
| Authors | Wang, Jiadong Aroumougame, Asaithamby Lobrich, Markus Li, Yujing Chen, David Chen, Junjie Gong, Zihua |
| Affiliation | Peking Univ, Inst Syst Biomed, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China. Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. Univ Texas SW Med Ctr Dallas, Dept Radiat Biol, Dallas, TX 75390 USA. Tech Univ Darmstadt, Radiat Biol & DNA Repair Lab, D-64287 Darmstadt, Germany. |
| Keywords | PTIP Artemis 53BP1 BRCA1 DNA repair PARP inhibition LYSINE-4 METHYLTRANSFERASE COMPLEX REPLICATION CHECKPOINT CONTROL BRCA-MUTATED BREAST END RESECTION PROTEIN RECOMBINATION BINDING TOPBP1 RIF1 AUTOPHOSPHORYLATION |
| Issue Date | 2014 |
| Publisher | genes development |
| Citation | GENES & DEVELOPMENT.2014,28,(24),2693-2698. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/188696 |
| ISSN | 0890-9369 |
| DOI | 10.1101/gad.252478.114 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 基础医学院 |
