Figure 4.

Schematic Representations of Mechanisms Underlying CFSs

(A) The microhomology-mediated mechanism is predominantly involved in rearrangement processes at CFSs. (a) Detailed analysis of the nucleotide-sequence content flanking the breakpoints demonstrated that junctions with microhomologies (pink) are predominantly observed, compared with junctions without any homology (sky blue). Junctions with extended homologies (green) underlying NAHR are infrequent. (b) Schematic representation of MMEJ. (c) Schematic representation of NAHR.

(B) Multiple factors affecting DNA-replication kinetics collectively contribute to fragility as a common molecular basis. The breakpoint-clustering region at CFSs is flanked by the high-flexibility peaks and the R/G band boundaries. The breakpoint-clustering region coincides with the late-replicating region and is embedded in large LADs.