Journal
TRENDS IN GENETICS
Volume 28, Issue 6, Pages 295-302Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tig.2012.02.006
Keywords
fragile sites; replication; cancer; genomic instability; DNA damage; dormant origins
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Common fragile sites (CFSs) were characterized almost 30 years ago as sites undergoing genomic instability in cancer. Recently, in vitro studies have found that oncogene-induced replication stress leads to CFS instability. In vivo, CFSs were found to be preferentially unstable during early stages of cancer development and to leave a unique signature of instability. It is now increasingly clear that, along the spectrum of replication features characterizing CFSs, failure of origin activation is a common feature. This and other features of CFSs, together with the replication stress characterizing early stages of cancer development, lead to incomplete replication that results in genomic instability preferentially at CFSs. Here, we review the shared and unique characteristics of CFSs, their underlying causes and their implications, particularly with respect to the development of cancer.
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