Heterogeneous expression of Ku70 in human tissues is associated with morphological and functional alterations of the nucleus

Eun Kyung Choi, Yeon Hee Lee, Yong Seok Choi, Hyock Man Kwon, Mi Sun Choi, Jae Y. Ro, Su Kil Park, Eunsil Yu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Ku70 is a subunit of DNA-protein kinase complex and involved in diverse intranuclear events including the repair of double-stranded DNA breaks. Ku70 is rich in the interphase nucleus of cultured cells. In human tissues, however, the distribution of Ku70 has not yet been systematically examined. To characterize the difference of Ku70 distribution between cells of human tissues and cultured cells, the expression of Ku70 was examined in various normal and neoplastic human tissues by immunohistochemistry and immunoblot. In addition, the role of Ku70 in the cellular response against ionizing radiation (IR) was analysed in fibroblasts after exposure to 5 Gy IR and apoptotic indices were examined in Ku70-overexpressed fibroblasts from an ataxia telangiectasia patient and in normal fibroblasts, before and after irradiation. In contrast to cultured cells, Ku70 was not detected in some interphase cells of human tissues and was distributed heterogeneously, even in the same nucleus. Ku70 expression was strikingly low in terminally differentiated cells such as neutrophils, eosinophils, glomerular capillary endothelial cells and fibroblasts, and was absent in spermatids. In spermatocytes, Ku70 was tightly integrated with chromosome filaments, unlike other somatic cells under mitosis. After exposure to IR, Ku70 expression was nót increased in ataxia telangiectasia fibroblasts, but was significantly increased in normal fibroblasts. Most of the increased Ku70 was of soluble nuclear protein fraction. Furthermore, overexpression of Ku70 increased radiation resistance both in ataxia telangiectasia fibroblasts and normal fibroblasts. The presented data indicate that the distribution of Ku70 in cells of human tissues is closely associated with the cell cycle, cellular differentiation, nuclear shape and the process of repair of DNA damage caused by IR.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalJournal of Pathology
Volume198
Issue number1
DOIs
StatePublished - Sep 2002

Keywords

  • Apoptosis
  • Ataxia telangiectasia
  • DNA repair
  • Fibroblast
  • Human tissue
  • Ionizing radiation
  • Ku70
  • Nucleus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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