SMC1 inhibition results in FRA3B expression but has no effect on its delayed replication

Maria Luisa Focarelli, Cristina Montagna, Roberto Colombo, Thomas Ried, Paolo Vezzoni, Antonio Musio

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Cellular processes involved in fragile site expression have been investigated by studying the effect on the replication pattern of the commonest fragile site FRA3B of RNA interference (RNAi)-mediated sister maintenance chromosome 1 (SMC1) inhibition in normal human fibroblasts. Replication timing of FRA3B in G2 was studied by bromodeoxyuridine (BrdU) labeling for the final 2 h of cell culture whereas in the S phase was investigated by a fluorescence in situ hybridization (FISH)-based approach through the analysis of clones spanning the FRA3B region. Results showed that FRA3B is normally late replicated even though it is not expressed in untreated cells. On the other hand, SMC1 inhibition leads to FRA3B expression even if the percent of late replicated cells is comparable to control cells. These results obtained by analysing the commonest fragile site suggest that SMC1 plays a role in protecting late replicating regions from stresses occurring in the final steps of genome replication and that delayed replication is necessary but not sufficient for inducing fragile site expression.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume595
Issue number1-2
DOIs
StatePublished - Mar 20 2006

Keywords

  • Delayed replication
  • FRA3B
  • Fragile sites
  • SMC1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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