Cells with dysfunctional telomeres are susceptible to reactive oxygen species hydrogen peroxide via generation of multichromosomal fusions and chromosomal fragments bearing telomeres

Seon Rang Woo, Jeong Eun Park, Kyoung Mi Juhn, Yeun Jin Ju, Jaemin Jeong, Chang Mo Kang, Hyun Jin Yun, Mi Yong Yun, Hyun Jin Shin, Hyun Yoo Joo, Eun Ran Park, In Chul Park, Sung Hee Hong, Sang Gu Hwang, Haekwon Kim, Myung Haing Cho, Sang Hoon Kim, Gil Hong Park, Kee Ho Lee

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

During genotoxic stress, reactive oxygen species hydrogen peroxide (H 2O 2) is a prime mediator of the DNA damage response. Telomeres function both to assist in DNA damage repair and to inhibit chromosomal end-to-end fusion. Here, we show that telomere dysfunction renders cells susceptible to H 2O 2, via generation of multichromosomal fusion and chromosomal fragments. H 2O 2 caused formation of multichromosomal end-to-end fusions involving more than three chromosomes, preferentially when telomeres were erosive. Interestingly, extensive chromosomal fragmentation (yielding small-sized fragments) occurred only in cells exhibiting such multichromosomal fusions. Telomeres were absent from fusion points, being rather present in the small fragments, indicating that H 2O 2 cleaves chromosomal regions adjacent to telomeres. Restoration of telomere function or addition of the antioxidant N-acetylcysteine prevented development of chromosomal aberrations and rescued the observed hypersensitivity to H 2O 2. Thus, chromosomal regions adjacent to telomeres become sensitive to reactive oxygen species hydrogen peroxide when telomeres are dysfunctional, and are cleaved to produce multichromosomal fusions and small chromosomal fragments bearing the telomeres.

Original languageEnglish
Pages (from-to)204-210
Number of pages7
JournalBiochemical and biophysical research communications
Volume417
Issue number1
DOIs
Publication statusPublished - 2012 Jan 6

Keywords

  • Chromosomal fragment
  • H O
  • Multichromosomal fusion
  • Telomerase
  • Telomere

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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