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
Artikel, Zweitveröffentlichung, Verlagsversion
Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2021 |
| Autor(en): | Wang, Jiadong ; Aroumougame, Asaithamby ; Löbrich, Markus ; Li, Yujing ; Chen, David ; Chen, Junjie ; Gong, Zihua |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | PTIP associates with Artemis to dictate DNA repair pathway choice |
| Sprache: | Englisch |
| Publikationsjahr: | 2021 |
| Publikationsdatum der Erstveröffentlichung: | 2014 |
| Verlag: | Cold Spring Harbor Laboratory Press |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Genes & Development |
| Jahrgang/Volume einer Zeitschrift: | 28 |
| (Heft-)Nummer: | 24 |
| DOI: | 10.26083/tuprints-00018930 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/18930 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichungsservice |
| Kurzbeschreibung (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: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-189301 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair |
| Hinterlegungsdatum: | 12 Aug 2021 12:09 |
| Letzte Änderung: | 17 Aug 2021 06:28 |
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