Abstract
Common fragile sites have been mapped primarily in lymphocytes, but recent analyses show that the setting of these sites relies on cell type–dependent replication programs. Using a new approach, we molecularly mapped common fragile sites in human fibroblasts and showed that commitment to fragility depends on similar replication features in fibroblasts and lymphocytes, although different loci are committed in each cell type. Notably, the common fragile sites that we identified overlapped heretofore unexplained deletion clusters observed in tumors.
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Acknowledgements
We thank R. Rothstein, A. Letessier and H. Técher for critical reading of the manuscript. The M.D. team is supported by Institut National du Cancer (INCa) (2009-1-PLBIO-10-IC-1), by Agence Nationale de la Recherche (ANR-09-GENO-000/repinsCFS) and by Association pour la Recherche sur le Cancer (Subvention Libre n° SL220100601348 and Equipements mi-lourds n° 8514). B.L.T. is supported by a fellowship from INCa.
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B.D. conducted the R-banding analyses; B.L.T., A.M.L. and O.B. carried out and analyzed the FISH experiments; G.A.M. did the Repli-Seq analyses; B.L.T., O.B. and M.D. wrote the manuscript; M.D. and O.B. planned the project.
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Supplementary Figures 1–2, Supplementary Tables 1–3 and Supplementary Methods (PDF 481 kb)
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Le Tallec, B., Dutrillaux, B., Lachages, AM. et al. Molecular profiling of common fragile sites in human fibroblasts. Nat Struct Mol Biol 18, 1421–1423 (2011). https://doi.org/10.1038/nsmb.2155
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DOI: https://doi.org/10.1038/nsmb.2155
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