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

9 Citations (Scopus)

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 1 2017

Fingerprint

Ionizing Radiation
DNA Repair
Cell Cycle
DNA
Nonionizing Radiation
Double-Stranded DNA Breaks
G2 Phase
Cell Division
DNA Damage
Neoplasms
Up-Regulation
Radiation
Apoptosis

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

14-3-3σ contributes to radioresistance by regulating DNA repair and cell cycle via PARP1 and CHK2. / Chen, Yifan; Li, Zhaomin; Dong, Zizheng; Beebe, Jenny; Yang, Ke; Fu, Liwu; Zhang, Jian-Ting.

In: Molecular Cancer Research, Vol. 15, No. 4, 01.04.2017, p. 418-428.

Research output: Contribution to journalArticle

Chen, Yifan ; Li, Zhaomin ; Dong, Zizheng ; Beebe, Jenny ; Yang, Ke ; Fu, Liwu ; Zhang, Jian-Ting. / 14-3-3σ contributes to radioresistance by regulating DNA repair and cell cycle via PARP1 and CHK2. In: Molecular Cancer Research. 2017 ; Vol. 15, No. 4. pp. 418-428.
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