Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats.
There is an emerging consensus that secondary structures of DNA have the potential for genomic instability. Palindromic AT-rich repeats (PATRRs) are a characteristic sequence identified at each breakpoint of the recurrent constitutional t(11;22) and t(17;22) translocations in humans, named PATRR22 (approximately 600 bp), PATRR11 (approximately 450 bp) and PATRR17 (approximately 190 bp). The secondary structure-forming propensity in vitro and the instability in vivo have been experimentally evaluated for various PATRRs that differ regarding their size and symmetry. At physiological ionic strength, a cruciform structure is most frequently observed for the symmetric PATRR22, less often for the symmetric PATRR11, but not for the other PATRRs. In wild-type E. coli, only these two PATRRs undergo extensive instability, consistent with the relatively high incidence of the t(11;22) in humans. The resultant deletions are putatively mediated by central cleavage by the structure-specific endonuclease SbcCD, indicating the possibility of a cruciform conformation in vivo. Insertion of a short spacer at the centre of the PATRR22 greatly reduces both its cruciform extrusion in vitro and instability in vivo. Taken together, cruciform extrusion propensity depends on the length and central symmetry of the PATRR, and is likely to determine the instability that leads to recurrent translocations in humans.
Kogo
Hiroshi
H
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Inagaki
Hidehito
H
Ohye
Tamae
T
Kato
Takema
T
Emanuel
Beverly S
BS
Kurahashi
Hiroki
H
D020856:AT Rich Sequence; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002892:Chromosomes, Human, Pair 22; D045566:DNA, Cruciform / Q000737:chemistry*; D003851:Deoxyribonucleases / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D009690:Nucleic Acid Conformation; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014178:Translocation, Genetic
D045566:DNA, Cruciform; D029968:Escherichia coli Proteins; C489229:SbcC protein, E coli; D003851:Deoxyribonucleases