Figure 3.

Differential DNA replication. (A) Underreplication results from two effects: absence of replication origins and initiation within a domain coupled with impaired progression of replication forks initiating from flanking origins (arrows indicate direction of fork progression). Replication forks are destabilized within underreplicated regions and can lead to double-stranded DNA breaks (red circles). These can lead to deletions or rearrangements in the region. Array-based comparative genome hybridization (aCGH) analysis of an underreplicated site indicates decreased copy number relative to overall ploidy. aCGH data are modified from Sher et al. (2012). (B) In endocycling follicle cells, developmentally programmed gene amplification occurs through repeated replication origin firing followed by bidirectional fork progression away from the origin (arrows indicate direction of fork progression). Rereplication can lead to fork collisions, resulting in double-strand DNA breaks (red circles). aCGH analysis of an amplified site indicates a gradient of increased copy number relative to overall ploidy spanning 100 kb, with the highest copy number at the origin of replication. aCGH data are modified from Kim et al. (2011).