Figure 1.

Model for mitotic DNA synthesis (MiDAS) at the FMR1 locus. FM alleles with stalled replication forks that have not been resolved by the time mitosis begins are cleaved by the SLX1/SLX4 nuclease to generate a one-ended DSB. After end resection to generate a 3′ overhang, binding of RAD51 allows the exposed 3′ end to invade a homologous template, likely a sister chromatid. Conservative DNA synthesis then occurs in a POLD3-dependent fashion to complete replication [48]. Failure to initiate this process results in the formation of ultrafine bridges and the high frequency loss of the affected X chromosome [26,48], while failure to complete MiDAS results in fragile site expression [48].