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BioMed Research International
Volume 2013 (2013), Article ID 730714, 9 pages
Review Article

Genome Instability at Common Fragile Sites: Searching for the Cause of Their Instability

Section of Molecular Epidemiology, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy

Received 27 April 2013; Accepted 7 August 2013

Academic Editor: Abbas Dehghan

Copyright © 2013 Annapaola Franchitto. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Common fragile sites (CFS) are heritable nonrandomly distributed loci on human chromosomes that exhibit an increased frequency of chromosomal breakage under conditions of replication stress. They are considered the preferential targets for high genomic instability from the earliest stages of human cancer development, and increased chromosome instability at these loci has been observed following replication stress in a subset of human genetic diseases. Despite their biological and medical relevance, the molecular basis of CFS fragility in vivo has not been fully elucidated. At present, different models have been proposed to explain how instability at CFS arises and multiple factors seem to contribute to their instability. However, all these models involve DNA replication and suggest that replication fork stalling along CFS during DNA synthesis is a very frequent event. Consistent with this, the maintenance of CFS stability relies on the ATR-dependent checkpoint, together with a number of proteins promoting the recovery of stalled replication forks. In this review, we discuss mainly the possible causes that threaten the integrity of CFS in the light of new findings, paying particular attention to the role of the S-phase checkpoint.