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Aphidicolin-Induced FRA3B Breakpoints Cluster in Two Distinct Regions
Authors:Liang Wang  William Paradee  Chadwick Mullins  Ravi Shridhar  Rita Rosati  Charles M Wilke  Thomas W Glover  David I Smith
Institution:aDivision of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Foundation, Rochester, Minnesota, 55905;bHoward Hughes Medical Institute, Emory University School of Medicine, Atlanta, Georgia;cKarmanos Cancer Institute, Division of Hematology/Oncology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan;dDepartments of Pediatrics and Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan
Abstract:The common fragile site at chromosomal band 3p14.2 (FRA3B) is the most sensitive single site in the human genome to induced chromosomal lesions. This fragile site may predispose chromosome 3p to breakage that is commonly observed in lung, renal, and many other cancers. We previously used aphidicolin induction of FRA3B expression in a chromosome 3-only somatic cell hybrid to generate a series of hybrids with breakpoints in the 3p14.2 region. These breakpoints were localized to two distinct clusters, separated by 200 kb, that lie on either side of a region of frequent breakage within FRA3B as observed by FISH analysis. Seven proximal aphidicolin-induced breakpoints were localized at or near the end of a THE element. The THE-1 element is flanked by LINE andAlurepetitive elements. The eight distal aphidicolin-induced breakpoints clustered in a region capable of forming multiple hairpin-like structures. Thus repetitive elements and hairpin-like structures may be responsible for chromosome fragility in this region.
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