Fragile sites

Trinucleotide Repeat Expansion DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats, [nih]... 

It has also been proposed that Parkin is a tumor suppressor gene [240]. It is included in the fragile site FRA6E [241] and down-regulation of Parkin protein due to exon duplication or deletions has been observed in several cancer cell lines and tumors [241]. 

Denison, S. R., et al.. Alterations in the common fragile site gene Parkin in ovarian and other cancers. 

Recently, it has been reported that the expression of several miRNAs are altered in a variety of human cancers, suggesting potential roles of miRNAs in tumorigenesis (37). Calin et al. (38) showed that more than 50% of miRNAs were located in cancer-associated genomic regions or in fragile sites. In fact, miR-15a and miR-16 genes exist... 

Calin GA, Sevignani C, Dumitru CD et al. Human mieroRNA genes are frequently located at fragile sites and genomic regions involved in eaneers. Proc Natl Acad Sci USA 2004 101 2999-3004. 

Sutherland GR Fragile sites on human chromosomes demonstration of their dependence on the type tissue culture medium. Science 197 265-266,1977. 

At least nine fragile sites are present in human chromosomes. The fragility refers to chromosomal sites that break easily in the presence of certain compounds such as aphidocolin, methotrexate, and high doses of caffeine (Sutherland, 1979a, b). These sites are generally (GCC) stretches and in most cases are protected if folate, thymidine, or folinic acid is in the medium (Sutherland, 1979a, b,... 

Sutherland GR (1979a) Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culture. Am J Hum Genet 31 125-135... 

Casper AM, Nghiem P, Arlt ME, Glover TW. ATR regulates fragile site stability. Cell 2002 111 779-789. 

Durkin SG, Arlt ME, Hewlett NG, Glover TW. Depletion of CHKl, but not CHK2, induces chromosomal instability and breaks at common fragile sites. Oncogene 2006 25 4381-4388. 

El Achkar E, Gerbault-Seureau M, Muleris M, Dutrillaux B, Debatisse M. Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites. Proc. Natl. Acad. Sci. U.S.A. 2005 102 18069-18074. 

Le Beau MM, Rassool FV, Neilly ME, Espinosa R 3rd, Glover TW, Smith DI, McKeithan TW. Replication of a common fragile site, ERA3B, occurs late in S phase and is delayed further upon induction implications for the mechanism of fragile site induction. Hum. Mol. Genet. 1998 7 755-761. 

Although fragile X syndrome is classified a Mendelian dominant sex-linked disorder, it does not behave as a classically dominant gene inherited disease. Only about 80% of males and 35% of females who carry the mutation and a fragile site suffer from mental retardation. For many years it remained a mystery how both men and women could carry a fragile X chromosome and be unaffected. 

G., and Debatisse, M. (1997) Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to amplicons. Cell 89 215-225. 

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