Bora downregulation results in radioresistance by promoting repair of double strand breaks

Junmei Cairns, Yi Peng, Vivien C. Yee, Zhenkun Lou, Liewei M Wang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Following DNA double-strand breaks cells activate several DNA-damage response protein kinases, which then trigger histone H2AX phosphorylation and the accumulation of proteins such as MDC1, p53-binding protein 1, and breast cancer gene 1 at the damage site to promote DNA double-strand breaks repair. We identified a novel biomarker, Bora (previously called C13orf34), that is associated with radiosensitivity. In the current study, we set out to investigate how Bora might be involved in response to irradiation. We found a novel function of Bora in DNA damage repair response. Bora down-regulation increased colony formation in cells exposed to irradiation. This increased resistance to irradiation in Bora-deficient cells is likely due to a faster rate of double-strand breaks repair. After irradiation, Bora-knockdown cells displayed increased G2-M cell cycle arrest and increased Chk2 phosphorylation. Furthermore, Bora specifically interacted with the tandem breast cancer gene 1 C-terminal domain of MDC1 in a phosphorylation dependent manner, and overexpression of Bora could abolish irradiation induced MDC1 foci formation. In summary, Bora may play a significant role in radiosensitivity through the regulation of MDC1 and DNA repair.

Original languageEnglish (US)
Article numbere0119208
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 5 2015

Fingerprint

radiation resistance
Repair
Down-Regulation
irradiation
Phosphorylation
Irradiation
Double-Stranded DNA Breaks
Neoplasm Genes
Radiation Tolerance
DNA
phosphorylation
DNA Repair
DNA Damage
DNA damage
breast neoplasms
G2 Phase Cell Cycle Checkpoints
Breast Neoplasms
Genes
cells
Histones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bora downregulation results in radioresistance by promoting repair of double strand breaks. / Cairns, Junmei; Peng, Yi; Yee, Vivien C.; Lou, Zhenkun; Wang, Liewei M.

In: PLoS One, Vol. 10, No. 3, e0119208, 05.03.2015.

Research output: Contribution to journalArticle

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