Common fragile sites: mechanisms of instability revisited

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 chromoso...

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Bibliographic Details
Published in:Trends in genetics 2012-01, Vol.28 (1), p.22-32
Main Authors: Debatisse, Michelle, Le Tallec, Benoît, Letessier, Anne, Dutrillaux, Bernard, Brison, Olivier
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chromosome Fragile Sites
DNA - genetics
DNA - metabolism
DNA Replication
Epigenesis, Genetic
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Genomic Instability
Humans
Medical Education
Molecular and cellular biology
Transcription, Genetic
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Summary: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.
ISSN:0168-9525
DOI:10.1016/j.tig.2011.10.003