title: The common fragile site FRA16D and its associated gene WWOX are highly conserved in the mouse at Fra8E1.
abstract: Recently, several common fragile sites (CFSs) have been cloned and characterized, including the two most frequently observed in the human population, FRA3B and FRA16D. In addition to their high frequency of breakage, FRA3B and FRA16D colocalize with genes crossing large regions of breakage. At FRA3B, the fragile histidine triad (FHIT) gene spans more than 1 Mb, and at FRA16D, the WWOX gene spans more than 750 kb. It has also been shown that in Mus musculus, a CFS Fra14A2 and the mouse Fhit gene are conserved in the orthologous region of the genome. In this study, we positioned the ortholog to WWOX (Wox1) at chromosome band 8E1 in the mouse genome. To determine whether, like Fra14A2 and Fhit, Fra8E1 and Wox1 colocalized in the mouse, we prepared bacterial and yeast artificial chromosome probes, and we hybridized them to aphidicolin-treated mouse metaphase chromosomes. Our data demonstrate that Wox1 colocalizes with Fra8E1. Furthermore, the sequence from this region, including introns, is highly conserved over at least a 100-kb region. This evolutionary conservation suggests that the two most active CFSs share many features, and that CFSs and their associated genes may be necessary for cell survival.
authors.affiliation: Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Cancer Center, Rochester, Minnesota 55905, USA.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Krummel
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Denison
authors.forename: Eric
authors.initials: E
authors.lastname: Calhoun
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Phillips
authors.forename: David I
authors.initials: DI
authors.lastname: Smith
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics*; D020451:Contig Mapping / Q000379:methods; D005091:Exons / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007438:Introns / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D009363:Neoplasm Proteins / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics; D013154:Spleen / Q000166:cytology; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; C428130:Wwox protein, mouse