title: Updating the mechanisms of common fragile site instability: how to reconcile the different views?
abstract: Common fragile sites (CFSs) are large chromosomal regions long identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs came from their key role in the formation of DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was notably correlated with the appearance of genome instability in precancerous lesions and during tumor progression. Identification of the molecular mechanisms responsible for their instability therefore represents a major challenge. A number of data show that breaks result from mitotic entry before replication completion but the mechanisms responsible for such delayed replication of CFSs and relaxed checkpoint surveillance are still debated. In addition, clues to the molecular events leading to breakage just start to emerge. We present here the results of recent reports addressing these questions.
authors.affiliation: Institut Curie, Centre de Recherche, 26 rue d'Ulm, 75248, Paris Cedex 05, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Le Tallec
authors.forename: Stéphane
authors.initials: S
authors.lastname: Koundrioukoff
authors.forename: Therese
authors.initials: T
authors.lastname: Wilhelm
authors.forename: Anne
authors.initials: A
authors.lastname: Letessier
authors.forename: Olivier
authors.initials: O
authors.lastname: Brison
authors.forename: Michelle
authors.initials: M
authors.lastname: Debatisse
mesh_terms: D000818:Animals; D002453:Cell Cycle; D043283:Chromosome Fragile Sites; D004249:DNA Damage; D004261:DNA Replication; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology