DNA damage response defect in Williams-Beuren syndrome

David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre Simon Rohrlich

Research output: Contribution to journalArticlepeer-review


Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non-Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways. Cell proliferation, cell cycle analysis, γ-H2A.X induction, and expression of DNA damage response proteins were investigated upon exposure to genotoxic treatments in WBS patient-derived primary fibroblasts and in the 293T cell line treated with specific siRNAs targeting RFC2, GTF2I and BAZ1B. An impaired hydroxyurea-induced phosphorylation of CHK1 was observed in the WBS cells. However, this defective DNA damage response was not associated with an increased sensitivity to genotoxic agents. In addition, depletion of RFC2, GTF2I and BAZ1B using specific siRNAs did not have a significant impact on the DNA damage response in 293T cells. Our results highlight that the ATR-dependent DNA damage response is impaired in WBS patient cells but is also dispensable for viability when these cells undergo a genotoxic stress. The mechanism by which the ATR pathway is impaired in WBS warrants elucidation through further investigation.

Original languageEnglish
Pages (from-to)622-628
Number of pages7
JournalInternational Journal of Molecular Medicine
Issue number3
Publication statusPublished - Mar 1 2017


  • 7q11.23
  • BAZ1B
  • Cancer
  • DNA damage
  • GTF2I
  • Non-Hodgkin's lymphoma
  • Predisposition
  • RFC2
  • Williams syndrome
  • Williams-Beuren syndrome

ASJC Scopus subject areas

  • Genetics


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