Fragile sites in human chromosomes as regions of late-replicating DNA

We review data indicating that fragile sites in chromosomes of humans, Drosophila and Microtus represent regions where DNA is late-replicating in the cell cycle. We suggest that rare fragile sites in human chromosomes represent cis-acting alterations to DNA that confer or accentuate late replication at that site. The possible connection between late replication and the fragile X syndrome is also discussed.