14-3-3σ contributes to radioresistance by regulating DNA repair and cell cycle via PARP1 and CHK2

Yifan Chen, Zhaomin Li, Zizheng Dong, Jenny Beebe, Ke Yang, Liwu Fu, Jian Ting Zhang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

14-3-3σ has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3σ contributes to these resistances via inhibiting apoptosis and arresting cells in G2-Mphase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3σ causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2-M phase following DNA-damaging treatments. We showed that 14-3-3σ contributed to ionizing radiation (IR) resistance by arresting cancer cells in G2-Mphase following IR and by increasing non-homologous end joining (NHEJ) repair of the IR-induced DNA double strand breaks (DSB). The increased NHEJ repair activity was due to 14-3-3σ-mediated upregulation of PARP1 expression that promoted the recruitment of DNA-PKcs to the DNA damage sites for repair of DSBs. On the other hand, the increased G2-M arrest following IR was due to 14-3-3σ-induced Chk2 expression.

Original languageEnglish (US)
Pages (from-to)418-428
Number of pages11
JournalMolecular Cancer Research
Volume15
Issue number4
DOIs
StatePublished - Apr 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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