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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.
In: Genes & Development, 2014, 28 (24)
doi: 10.26083/tuprints-00018930
Article, Secondary publication, Publisher's Version

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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: 2021
Creators: Wang, Jiadong ; Aroumougame, Asaithamby ; Löbrich, Markus ; Li, Yujing ; Chen, David ; Chen, Junjie ; Gong, Zihua
Type of entry: Secondary publication
Title: PTIP associates with Artemis to dictate DNA repair pathway choice
Language: English
Date: 2021
Year of primary publication: 2014
Publisher: Cold Spring Harbor Laboratory Press
Journal or Publication Title: Genes & Development
Volume of the journal: 28
Issue Number: 24
DOI: 10.26083/tuprints-00018930
URL / URN: https://tuprints.ulb.tu-darmstadt.de/18930
Corresponding Links:
Origin: Secondary publication service
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.

Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-189301
Classification DDC: 500 Science and mathematics > 570 Life sciences, biology
Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 12 Aug 2021 12:09
Last Modified: 17 Aug 2021 06:28
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