FIG 3.

Replicating fragile sites. (A) FRA3B. In lymphoblasts, replication forks travel from large distances outside the fragile site inner core, and there is no activation of internal origins. At the end of the S phase, the whole locus is frequently underreplicated and therefore prone to breakage. In fibroblasts, the activation of several internal replication origins allows completion of replication of the locus, decreasing its fragility. (Based on data from reference 61.) (B) FRAXA. Replication proceeds from three origins within the locus. The fork traveling from ORI II is stalled by the CGG trinucleotide repeat expansion on the lagging strand template. ORI III, traveling in the other orientation, is less affected since the CGG sequence is on the leading strand template (67, 68).