Article thumbnail

The Werner syndrome helicase protein is required for cell proliferation, immortalization, and tumorigenesis in Scaffold Attachment Factor B1 deficient mice

By Sophie Lachapelle, Steffi Oesterreich and Michel Lebel


Werner syndrome (WS) is a rare disorder characterized by the premature onset of several pathologies associated with aging. The gene responsible for WS codes for a RecQ-type DNA helicase and is believed to be involved in different aspects of DNA repair, replication, and transcription. We recently identified the Scaffold attachment factor B1 (SAFB1) as a potential interactants in human cells. SAFB1 is a multifunctional protein that binds both nucleic acids and is involved in the attachment of chromatin to the nuclear matrix, transcription, and stress response. Mice lacking SAFB1 exhibit developmental abnormalities in their lungs, high incidence of perinatal lethality, and adults develop different types of tumors. Mouse embryonic fibroblasts from Safb1-null animals are immortalized in culture. In this study, mice with a mutation in the helicase domain of the Wrn gene were crossed to Safb1-null mice. Double homozygous mutant mice exhibited increased apoptosis, a lower cell proliferation rate in their lungs and a higher incidence of perinatal death compared to Safb1-null mice. Few double homozygous mutants survived weaning and died before the age of six months. Finally, mouse embryonic fibroblasts lacking a functional Wrn helicase inhibited the immortalization of Safb1-null cells. These results indicate that an intact Wrn protein is required for immortalization and tumorigenesis in Safb1-null mice

Topics: Research Paper
Publisher: Impact Journals LLC
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. A deletion within the murine Werner syndrome
  2. Bohr proteins Res.
  3. Fang SA. markers functional
  4. Genetic poly(ADP‐ribose) complex J
  5. Homologous recombination resolution defect
  6. (2009). Katakura al. programs of human normal diploid
  7. Kolvraa cooperate TRF1
  8. (2006). Massip M. cardiac the Werner syndrome gene homologue. Exp Gerontol.
  9. (1998). McConnell cyclin‐dependent kinases induce features of replicative 2011,
  10. Przybylski specifically Biol.
  11. Riabowol K. Protein kinase C delta blocks immediate‐early gene
  12. Salk syndrome cultured skin fibroblasts: variegated translocation mosaicism.
  13. (1996). Scaffold/matrix‐attached regions: topological switches with multiple regulatory
  14. (2011). syndrome protein. I. DNA helicase and dna exonuclease 273:34139‐34144.
  15. Townson analysis of the estrogen receptor alpha corepressor scaffold attachment factor‐B1: identification of a potent transcriptional repression
  16. (2011).