title: Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily conserved but highly recombinogenic.
abstract: Common fragile sites are regions that show elevated susceptibility to DNA damage, leading to alterations that can contribute to cancer development. FRA3B, located at chromosome region 3p14.2, is the most frequently expressed human common fragile site, and allelic losses at FRA3B have been observed in many types of cancer. The FHIT gene, encompassing the FRA3B region, is a tumor-suppressor gene. To identify the features of FHIT/FRA3B that might contribute to fragility, sequences of the human FHIT and the flanking PTPRG gene were compared with those of murine Fhit and Ptprg. Human and mouse orthologous genes, FHIT and Fhit, are more highly conserved through evolution than PTPRG/Ptprg and yet contain more sequence elements that are exquisitely sensitive to genomic rearrangements, such as high-flexibility regions and long interspersed nuclear element 1s, suggesting that common fragile sites serve a function. The conserved AT-rich high-flexibility regions are the most characteristic of common fragile sites.
authors: Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
authors: Ayumi
authors: A
authors: Matsuyama
authors: Takeshi
authors: T
authors: Shiraishi
authors: Francesco
authors: F
authors: Trapasso
authors: Tamotsu
authors: T
authors: Kuroki
authors: Hansjuerg
authors: H
authors: Alder
authors: Masaki
authors: M
authors: Mori
authors: Kay
authors: K
authors: Huebner
authors: Carlo M
authors: CM
authors: Croce
mesh_terms: D017766:Acid Anhydride Hydrolases; D000818:Animals; D043283:Chromosome Fragile Sites; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005091:Exons; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D004247:DNA; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase