Cellular and Molecular Life Sciences

, Volume 71, Issue 23, pp 4507–4517 | Cite as

Replication fork recovery and regulation of common fragile sites stability

Multi-author review


The acquisition of genomic instability is a triggering factor in cancer development, and common fragile sites (CFS) are the preferential target of chromosomal instability under conditions of replicative stress in the human genome. Although the mechanisms leading to CFS expression and the cellular factors required to suppress CFS instability remain largely undefined, it is clear that DNA becomes more susceptible to breakage when replication is impaired. The models proposed so far to explain how CFS instability arises imply that replication fork progression along these regions is perturbed due to intrinsic features of fragile sites and events that directly affect DNA replication. The observation that proteins implicated in the safe recovery of stalled forks or in engaging recombination at collapsed forks increase CFS expression when downregulated or mutated suggests that the stabilization and recovery of perturbed replication forks are crucial to guarantee CFS integrity.


Genome instability Replication fork arrest Replication checkpoint Werner syndrome protein Common fragile sites 


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Copyright information

© Springer Basel 2014

Authors and Affiliations

  1. 1.Section of Molecular Epidemiology, Department of Environment and Primary PreventionIstituto Superiore di SanitàRomeItaly
  2. 2.Section of Experimental and Computational Carcinogenesis, Department of Environment and Primary PreventionIstituto Superiore di SanitàRomeItaly
  3. 3.Genome Stability GroupIstituto Superiore di SanitàRomeItaly

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