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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 (2014)
PTIP associates with Artemis to dictate DNA repair pathway choice.
In: Genes & development, 28 (24)
Artikel, Bibliographie

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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: 2014
Autor(en): Wang, Jiadong ; Aroumougame, Asaithamby ; Löbrich, Markus ; Li, Yujing ; Chen, David ; Chen, Junjie ; Gong, Zihua
Art des Eintrags: Bibliographie
Titel: PTIP associates with Artemis to dictate DNA repair pathway choice.
Sprache: Englisch
Publikationsjahr: 2014
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Genes & development
Jahrgang/Volume einer Zeitschrift: 28
(Heft-)Nummer: 24
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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.

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Radiation Biology and DNA Repair
Hinterlegungsdatum: 23 Dez 2014 08:50
Letzte Änderung: 03 Jul 2024 02:22
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