title: Common fragile sites: mechanisms of instability revisited.
abstract: Common fragile sites (CFSs) are large chromosomal regions prone to breakage upon replication stress that are considered a driving force of oncogenesis. CFSs were long believed to contain sequences blocking fork progression, thus impeding replication completion and leading to DNA breaks upon chromosome condensation. However, recent studies show that delayed completion of DNA replication instead depends on a regional paucity in initiation events. Because the distribution and the timing of these events are cell type dependent, different chromosomal regions can be committed to fragility in different cell types. These new data reveal the epigenetic nature of CFSs and open the way to a reevaluation of the role played by these sites in the formation of chromosome rearrangements found in tumors from different tissues.
authors.affiliation: Institut Curie, Centre de Recherche, 26 rue d'Ulm, 75248 Paris, France. michelle.debatisse@curie.fr
authors.forename: Michelle
authors.initials: M
authors.lastname: Debatisse
authors.forename: Benoît
authors.initials: B
authors.lastname: Le Tallec
authors.forename: Anne
authors.initials: A
authors.lastname: Letessier
authors.forename: Bernard
authors.initials: B
authors.lastname: Dutrillaux
authors.forename: Olivier
authors.initials: O
authors.lastname: Brison
mesh_terms: D000818:Animals; D043283:Chromosome Fragile Sites; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D044127:Epigenesis, Genetic; D042822:Genomic Instability; D006801:Humans; D014158:Transcription, Genetic
chemical_list: D004247:DNA