Chromosomal fragile site

[10] The CGG and AT-rich repeats characteristic of RFSs can form hairpins[11] and other non-B DNA structures that block replication forks and can result in breakage.

[12][13][14] DNA polymerase has been shown to pause at CTG and CGG triplet repeat sequences, which can result in continual expansion via slippage.

[18] CFS regions are highly conserved in mouse[19][20] and other species, including primates, cat, dog, pig, horse, cow, Indian mole rat, and yeast (for review, see [4]).

[4] Late-replication may be a result of formation of non-B DNA structures like hairpins and toroids that stall the replication fork in AT rich regions, analogous to the proposed mechanism of rare fragile site instability.

[22] Ataxia-telengiectasia and Rad3 Related (ATR) checkpoint kinase is required for maintaining stability of CFS under both stressed and normal replicating conditions.

For example, breakage at or near the FRA11b locus has been implicated in Jacobsen syndrome, which is characterized by loss of part of the long arm of chromosome 11 accompanied by mild mental retardation.

[31] Seckel syndrome, a genetic disease characterized by low levels of ATR, results in increased instability of chromosomes at fragile sites.

Silencing of the FMR1 Gene in Fragile X Syndrome
Silencing of the FMR1 gene in Fragile X syndrome . FMR1 co-localizes with a rare fragile site, visible here as a gap on the long arms of the X chromosome .