Abnormal Fibroblast Aging and DNA Replication in the Werner Syndrome

  • Yoshisada Fujiwara
  • Yoshio Kano
  • Masamitsu Ichihashi
  • Yoshinobu Nakao
  • Toshiharu Matsumura
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 190)

Abstract

Cell and DNA replicative potentials were studied in 10 strains of skin fibroblasts from unrelated patients with the Werner syndrome (WS) and in a progeric CRL 1277 strain. The lifespans of all WS strains and of CRL 1277 cells are greatly abbreviated in vitro, due to large fractions of non-cycling cells and the basic process of progressive clonal attenuation during Phase II. In some WS strains, the population-doubling rate per day and the cloning efficiency fluctuated concurrently in random fashion during the cellular aging process, indicating alternating successions of adaptively well and poorly growing clones, probably resulting from various chromosome translocations. No detectable defect in excision repair was found in WS or CRL 1277 cells. However, the rate of increase in the molecular weight of pulse-chased DNA involving overall rates of chain elongation and replicon fusion was retarded in WS and CRL 1277 cells. Also, pulse-labelled DNA in WS fibroblasts was less enriched in the nuclear matrix and was more slowly chased out than in normal cells. These results led us to postulate a misfiring or delayed initiation due to the sticky attachment of replicating DNA to the nuclear matrix in the replisomes of WS fibroblasts. A suggested model for abnormal DNA replication is presented and discussed to explain the loss of DNA and the chromosome abnormalities in WS cells. The abnormal DNA-synthetic profiles so derived appeared to be normalized in SV40-transformed PSV811 (WS) cells as were in gamma ray-transformed wild-type WI38CT-1 cells.

Keywords

Attenuation Cage Recombination Sedimentation Anemia 

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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Yoshisada Fujiwara
    • 1
  • Yoshio Kano
    • 1
  • Masamitsu Ichihashi
    • 2
  • Yoshinobu Nakao
    • 3
  • Toshiharu Matsumura
    • 4
  1. 1.Department of Radiation BiophysicsKobe University School of MedicineChuoku, Kobe 650Japan
  2. 2.Department of DermatologyKobe University School of MedicineChuoku, Kobe 650Japan
  3. 3.Department of Medicine IIIKobe University School of MedicineChuoku, Kobe 650Japan
  4. 4.Department of Pathobiochemical Cell Research, Institute of Medical ScienceUniversity of TokyoShirokanedai, Minato-ku, Tokyo 108Japan

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