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PTIP associates with Artemis to dictate DNA repair pathway choice.

Wang, Jiadong and Aroumougame, Asaithamby and Löbrich, Markus and Li, Yujing and Chen, David and Chen, Junjie and Gong, Zihua (2014):
PTIP associates with Artemis to dictate DNA repair pathway choice.
In: Genes & development, pp. 2693-8, 28, (24), ISSN 1549-5477, [Article]

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.

Item Type: Article
Erschienen: 2014
Creators: Wang, Jiadong and Aroumougame, Asaithamby and Löbrich, Markus and Li, Yujing and Chen, David and Chen, Junjie and Gong, Zihua
Title: PTIP associates with Artemis to dictate DNA repair pathway choice.
Language: English
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.

Journal or Publication Title: Genes & development
Volume: 28
Number: 24
Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 23 Dec 2014 08:50
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