The web supplement to
Pauline Chabosseau et al. 2011
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| Pyrimidine pool imbalance induced by BLM deficiency contributes to genetic instability in Bloom syndrome |
| Pauline Chabosseau1,2, Géraldine Buhagiar-Labarchède1,2,5, Rosine Onclercq-Delic1,2,5, Sarah Lambert1,2, Michelle Debatisse3,4, Olivier Brison3,4 and Mounira Amor-Guéret1,2 Nature Communications, 28 June 2011 |
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1Institut Curie, Centre de Recherche, Orsay, France. 2CNRS UMR 3348, Stress Génotoxiques et Cancer, Centre Universitaire, Bât. 110. 91405, Orsay, France. 3CNRS UMR 3244, Institut Curie, Centre de Recherche, Paris, France. 4Université Pierre et Marie Curie, 26 rue d’Ulm, 75248 Paris cedex 05, France. 5 These authors contributed equally to this work. |
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Abstract Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome (BS), which combines slowdown in replication speed, defective fork reactivation and high rates of sister chromatid exchange (SCE) with a general predisposition to cancer. BS is caused by mutations in the BLM gene encoding a RecQ helicase. We report that BLM deficiency is associated with a strong cytidine deaminase (CDA) defect leading to pyrimidine pool disequilibrium. In BLM-deficient cells, pyrimidine pool normalization leads to reduction of SCE frequency and is sufficient for full restoration of replication fork velocity but not the fork restart defect, thus identifying the part of the BS phenotype due to pyrimidine pool imbalance. This study provides new insights into the molecular basis of control of replication speed and of the genetic instability associated with Bloom syndrome. Nucleotide pool disequilibrium could be a general phenomenon in a large spectrum of pre-cancerous and cancer cells. |
| Download data: | ||
| Supplementary information (.xls) | Get it | |
| Affymetrix raw files (.CEL) | Get them (.zip) | |
| Affymetrix dataset (GC-RMA normalization) | Get them (.zip) |
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