Deficiency of Bloom syndrome helicase activity is radiomimetic

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

Research output: Contribution to journalArticle

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
StatePublished - 2008

Fingerprint

Bloom Syndrome
RecQ Helicases
DNA Helicases
Neoplasms
Sister Chromatid Exchange
Double-Stranded DNA Breaks
Ionizing Radiation
Heterografts
DNA Damage
Colorectal Neoplasms
Pharmacology
Mutation
Bloom syndrome protein
Growth

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Horowitz, D. P., Topaloglu, O., Zhang, Y., & Bunz, F. (2008). Deficiency of Bloom syndrome helicase activity is radiomimetic. Cancer Biology and Therapy, 7(11), 1783-1786.

Deficiency of Bloom syndrome helicase activity is radiomimetic. / Horowitz, David P.; Topaloglu, Ozlem; Zhang, Yonggang; Bunz, Fred.

In: Cancer Biology and Therapy, Vol. 7, No. 11, 2008, p. 1783-1786.

Research output: Contribution to journalArticle

Horowitz, DP, Topaloglu, O, Zhang, Y & Bunz, F 2008, 'Deficiency of Bloom syndrome helicase activity is radiomimetic', Cancer Biology and Therapy, vol. 7, no. 11, pp. 1783-1786.
Horowitz, David P. ; Topaloglu, Ozlem ; Zhang, Yonggang ; Bunz, Fred. / Deficiency of Bloom syndrome helicase activity is radiomimetic. In: Cancer Biology and Therapy. 2008 ; Vol. 7, No. 11. pp. 1783-1786.
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