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PTIP associates with Artemis to dictate DNA repair pathway choice

Wang, Jiadong ; Aroumougame, Asaithamby ; Löbrich, Markus ; Li, Yujing ; Chen, David ; Chen, Junjie ; Gong, Zihua (2021):
PTIP associates with Artemis to dictate DNA repair pathway choice. (Publisher's Version)
In: Genes & Development, 28 (24), pp. 2693-2698. Cold Spring Harbor Laboratory Press, ISSN 0890-9369, e-ISSN 1549-5477,
DOI: 10.26083/tuprints-00018930,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
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
Journal volume: 28
Number: 24
Publisher: Cold Spring Harbor Laboratory Press
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 12 Aug 2021 12:09
Last Modified: 12 Aug 2021 12:10
DOI: 10.26083/tuprints-00018930
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-189301
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/18930
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