Deficiency of Bloom syndrome helicase activity is radiomimetic

David P. Horowitz, Ozlem Topaloglu, Yonggang Zhang, Fred Bunz

Research output: Contribution to journalArticlepeer-review

Abstract

Bloom syndrome is caused by homozygous mutations in BLM, which encodes a RecQ DNA helicase. Patient-derived cells deficient in BLM helicase activity exhibit genetic instability - apparent cytogenetically as sister chromatid exchanges - and activated DNA damage signaling. In this report, we show that BLM-knockout colorectal cancer cells exhibited endogenous, ATM-dependent double-strand DNA break responses similar to those recently observed in Bloom syndrome patient-derived cells. Xenograft tumors established from BLM-deficient cancer cells were not radiosensitive, but exhibited growth impairment that was comparable to that of wild type tumors treated with a single, high dose of ionizing radiation. These results suggest that pharmacological inhibitors of BLM would have a radiomimetic effect, and that transient inhibition of BLM activity might be a viable strategy for anticancer therapy.

Original languageEnglish (US)
Pages (from-to)1783-1786
Number of pages4
JournalCancer Biology and Therapy
Volume7
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • ATM
  • BLM
  • Bloom syndrome
  • Cancer therapy
  • DNA damage
  • Gene targeting
  • Ionizing radiation
  • Xenografts

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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