Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts

Xiaodong Zhou, Wei Lin, Filemon K. Tan, Shervin Assassi, Mavin J. Fritzler, Xinjian Guo, Roozbeh Sharif, Tom Xia, Syeling Lai, Frank C. Arnett

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Introduction: Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I (topo I), which may associate with changes of cellular and topo I functions. Skin fibroblasts of patients with systemic sclerosis (SSc) exhibit profibrotic cellular changes. The aims of this study were to examine the catalytic function and sumoylation of topo I in the nuclei of SSc fibroblasts, a major cell type involved in the fibrotic process.Methods: Eleven pairs of fibroblast strains obtained from nonlesional skin biopsies of SSc patients and age/sex/ethnicity-matched normal controls were examined for catalytic function of nuclear topo I. Immunoprecipitation (IP)-Western blots were used to examine sumoylation of fibroblast topo I. Real-time quantitative RT-PCR was used to measure transcript levels of SUMO1 and COL1A2 in the fibroblasts.Results: Topo I in nuclear extracts of SSc fibroblasts generally showed a significantly lower efficiency than that of normal fibroblasts in relaxing equivalent amounts of supercoiled DNA. Increased sumoylation of topo I was clearly observed in 7 of 11 SSc fibroblast strains. Inhibition of SUMO1 with SUMO1 siRNA improved the catalytic efficiency of topo I in the SSc fibroblasts. In contrast, sumoylation of recombinant topo I proteins reduced their catalytic function.Conclusions: The catalytic function of topo I was decreased in SSc fibroblasts, to which increased sumoylation of topo I may contribute.

Original languageEnglish (US)
Article numberR128
JournalArthritis Research and Therapy
Volume13
Issue number4
DOIs
StatePublished - Aug 9 2011

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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