title: Chromosomal translocations and palindromic AT-rich repeats.
abstract: Repetitive DNA sequences constitute 30% of the human genome, and are often sites of genomic rearrangement. Recently, it has been found that several constitutional translocations, especially those that involve chromosome 22, take place utilizing palindromic sequences on 22q11 and on the partner chromosome. Analysis of translocation junction fragments shows that the breakpoints of such palindrome-mediated translocations are localized at the center of palindromic AT-rich repeats (PATRRs). The presence of PATRRs at the breakpoints indicates a palindrome-mediated mechanism involved in the generation of these constitutional translocations. Identification of these PATRR-mediated translocations suggests a universal pathway for gross chromosomal rearrangement in the human genome. De novo occurrences of PATRR-mediated translocations can be detected by PCR in normal sperm samples but not somatic cells. Polymorphisms of various PATRRs influence their propensity for adopting a secondary structure, which in turn affects de novo translocation frequency. We propose that the PATRRs form an unstable secondary structure, which leads to double-strand breaks at the center of the PATRR. The double-strand breaks appear to be followed by a non-homologous end-joining repair pathway, ultimately leading to the translocations. This review considers recent findings concerning the mechanism of meiosis-specific, PATRR-mediated translocations.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
mesh_terms: D020856:AT Rich Sequence; D043171:Chromosomal Instability; D056905:Chromosome Breakpoints; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D015894:Genome, Human; D006801:Humans; D055029:Inverted Repeat Sequences; D008297:Male; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D004247:DNA