title: Breakpoints of gross deletions coincide with non-B DNA conformations.
abstract: Genomic rearrangements are a frequent source of instability, but the mechanisms involved are poorly understood. A 2.5-kbp poly(purine.pyrimidine) sequence from the human PKD1 gene, known to form non-B DNA structures, induced long deletions and other instabilities in plasmids that were mediated by mismatch repair and, in some cases, transcription. The breakpoints occurred at predicted non-B DNA structures. Distance measurements also indicated a significant proximity of alternating purine-pyrimidine and oligo(purine.pyrimidine) tracts to breakpoint junctions in 222 gross deletions and translocations, respectively, involved in human diseases. In 11 deletions analyzed, breakpoints were explicable by non-B DNA structure formation. We conclude that alternative DNA conformations trigger genomic rearrangements through recombination-repair activities.
authors.affiliation: Institute of Biosciences and Technology, Center for Genome Research, Texas A&M University System Health Science Center, Texas Medical Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Albino
authors.initials: A
authors.lastname: Bacolla
authors.forename: Adam
authors.initials: A
authors.lastname: Jaworski
authors.forename: Jacquelynn E
authors.initials: JE
authors.lastname: Larson
authors.forename: John P
authors.initials: JP
authors.lastname: Jakupciak
authors.forename: Nadia
authors.initials: N
authors.lastname: Chuzhanova
authors.forename: Shaun S
authors.initials: SS
authors.lastname: Abeysinghe
authors.forename: Catherine D
authors.initials: CD
authors.lastname: O'Connell
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Robert D
authors.initials: RD
authors.lastname: Wells
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D019457:Chromosome Breakage / Q000235:genetics*; D015169:Colony Count, Microbial; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D015183:Restriction Mapping / Q000379:methods; D014158:Transcription, Genetic / Q000187:drug effects; D014169:Transformation, Bacterial; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D007544:Isopropyl Thiogalactoside; D004247:DNA