Palindrome-mediated chromosomal translocations in humans.
Recently, it has emerged that palindrome-mediated genomic instability contributes to a diverse group of genomic rearrangements including translocations, deletions, and amplifications. One of the best studied examples is the recurrent t(11;22) constitutional translocation in humans that has been well documented to be mediated by palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11. De novo examples of the translocation are detected at a high frequency in sperm samples from normal healthy males, but not in lymphoblasts or fibroblasts. Cloned breakpoint sequences preferentially form a cruciform configuration in vitro. Analysis of the junction fragments implicates frequent double-strand-breaks (DSBs) at the center of both palindromic regions, followed by repair through the non-homologous end joining (NHEJ) pathway. We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation.
Kurahashi
Hiroki
H
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan. kura@fujita-hu.ac.jp
Inagaki
Hidehito
H
Ohye
Tamae
T
Kogo
Hiroshi
H
Kato
Takema
T
Emanuel
Beverly S
BS
D020856:AT Rich Sequence; D019457:Chromosome Breakage; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D006801:Humans; D008297:Male; D008957:Models, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013094:Spermatozoa / Q000378:metabolism; D014178:Translocation, Genetic