Abstract
Fragile sites are genomic regions prone to deletions or other alterations during DNA replication. The reason for the susceptibility of these sites to damage may be simple: they contain few replication initiation sites. See Letter p.120 Some chromosomal locations, known as common fragile sites, are predisposed to breakage. These sites have pathological relevance because they are often associated with chromosomal translocations. An analysis of the replication dynamics along a 1.6-Mb region of FRA3B, a common fragile site in human lymphocytes that hosts the FHIT tumour suppressor gene, shows that, rather than breakage being due to replication stalling, FRA3B site fragility results from an unusually low density of replication origins. Surprisingly, fragility is cell-type-specific, which may have implications for current models of translocations and tumorigenesis.
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