title: Enhanced flexibility and aphidicolin-induced DNA breaks near mammalian replication origins: implications for replicon mapping and chromosome fragility.
abstract: Common fragile sites are chromosomal loci prone to breakage and rearrangement that can be induced by aphidicolin, an inhibitor of DNA polymerases. Within these loci, sites of preferential DNA breaks were proposed to correlate with peaks of enhanced DNA flexibility, the function of which remains elusive. Here we show that mammalian DNA replication origins are enriched in peaks of enhanced flexibility. This finding suggests that the search for these features may help in the mapping of replication origins, and we present evidence supporting this hypothesis. The association of peaks of flexibility with replication origins also suggests that some origins may associate with minor levels of fragility. As shown here, an increased sensitivity to aphidicolin was found near two mammalian DNA replication origins.
authors.affiliation: Unité de Génétique Somatique (URA CNRS 1960), Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. toledo@pop.salk.edu
authors.forename: F
authors.initials: F
authors.lastname: Toledo
authors.forename: A
authors.initials: A
authors.lastname: Coquelle
authors.forename: E
authors.initials: E
authors.lastname: Svetlova
authors.forename: M
authors.initials: M
authors.lastname: Debatisse
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology*; D002460:Cell Line; D019457:Chromosome Breakage; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000235:genetics; D002874:Chromosome Mapping; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004261:DNA Replication; D017404:In Situ Hybridization, Fluorescence; D018741:Replication Origin; D012093:Replicon; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D016590:Aphidicolin; D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase