A Werner syndrome protein homolog affects C. elegans development, growth rate, life span and sensitivity to DNA damage by acting at a DNA damage checkpoint

Se Jin Lee, Jong Sung Yook, Sung Min Han, Hyeon Sook Koo

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

A Werner syndrome protein homolog in C. elegans (WRN-1) was immunolocalized to the nuclei of germ cells, embryonic cells, and many other cells of larval and adult worms. When wrn-1 expression was inhibited by RNA interference (RNAi), a slight reduction in C. elegans life span was observed, with accompanying signs of premature aging, such as earlier accumulation of lipofuscin and tissue deterioration in the head. In addition, various developmental defects, including small, dumpy, ruptured, transparent body, growth arrest and bag of worms, were induced by RNAi. The frequency of these defects was accentuated by γ-irradiation, implying that they were derived from spontaneous or induced DNA damage. wrn-1(RNAi) worms showed accelerated larval growth irrespective of γ-irradiation, and pre-meiotic germ cells had an abnormal checkpoint response to DNA replication blockage. These observations suggest that WRN-1 acts as a checkpoint protein for DNA damage and replication blockage. This idea is also supported by an accelerated S phase in wrn-1(RNAi) embryonic cells. wrn-1(RNAi) phenotypes similar to those of Werner syndrome, such as premature aging and short stature, suggest wrn-1-deficient C. elegans as a useful model organism for Werner syndrome.

Original languageEnglish
Pages (from-to)2565-2575
Number of pages11
JournalDevelopment
Volume131
Issue number11
DOIs
Publication statusPublished - 2004 Jun 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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