PTIP associates with artemis to dictate DNA repair pathway choice

Jiadong Wang, Asaithamby Aroumougame, Markus Lobrich, Yujing Li, David Chen, Junjie Chenj, Zihua Gong

Research output: Contribution to journalArticle

55 Scopus citations

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 effec-tors, 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.

Original languageEnglish (US)
Pages (from-to)2693-2698
Number of pages6
JournalGenes and Development
Volume28
Issue number24
DOIs
StatePublished - Dec 15 2014

Keywords

  • 53BP1
  • Artemis
  • BRCA1
  • DNA repair
  • PARP inhibition
  • PTIP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Wang, J., Aroumougame, A., Lobrich, M., Li, Y., Chen, D., Chenj, J., & Gong, Z. (2014). PTIP associates with artemis to dictate DNA repair pathway choice. Genes and Development, 28(24), 2693-2698. https://doi.org/10.1101/gad.252478.114