Chromosomal end fusion resulting from telomere erosion increases susceptibility to radiation via multinucleation: Effect of p53

Yeun Jin Ju, Jeong Eun Park, Kyoung Mi Juhn, Jaemin Jeong, Miyong Yun, Myung Jin Park, Gil Hong Park, Kang Yell Choi, Myung Haeng Cho, Kwok Kin Wong, Won Bong Park, Kee Ho Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Loss of p53 tumor suppressor facilitates acquisition of telomerase activity. In fact, both p53 inactivation and telomerase activation are frequently found in human cancers. p53 inactivation, however, eliminates or attenuates the biological responses to telomerase inhibition and the eventual telomere erosion. We show that telomere erosion can increase the susceptibility to radiation, irrespective of p53 status. Both telomerase inhibition and critically shortened telomere with significant change of chromosomal end-to-end fusion were essential for the enhancement of radiosensitivity. The enhancement was correlated with greater formation of multinucleated cells. p53 inactivation did not eliminate the observed generation of chromosomal fusion and multinucleation, and the resulting increased susceptibility to radiation, as opposed to the previously proved role of p53 in mediating cellular responses to telomere dysfunction. The present findings suggest the importance of chromosomal end fusion in modulating radiosensitivity rather than p53 DNA damage signaling. Thus, the suggested anticancer radiotherapeutic strategy combined with telomerase inhibition could clinically be applicable to cancers, irrespective of p53 status.

Original languageEnglish
Pages (from-to)753-763
Number of pages11
JournalInternational journal of oncology
Volume29
Issue number4
Publication statusPublished - 2006 Oct

Keywords

  • Chromosome
  • Fusion
  • Radiosensitivity
  • Telomerase
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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