Chromosomal translocations and palindromic AT-rich repeats

Takema Kato, Hiroki Kurahashi, Beverly S. Emanuel

Research output: Contribution to journalReview article

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalCurrent Opinion in Genetics and Development
Volume22
Issue number3
DOIs
Publication statusPublished - 01-06-2012

Fingerprint

Genetic Translocation
Human Genome
Chromosomes, Human, Pair 22
Nucleic Acid Repetitive Sequences
Meiosis
Spermatozoa
Chromosomes
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

@article{0ab12125adc34407b1b96c1badbb1544,
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.",
author = "Takema Kato and Hiroki Kurahashi and Emanuel, {Beverly S.}",
year = "2012",
month = "6",
day = "1",
doi = "10.1016/j.gde.2012.02.004",
language = "English",
volume = "22",
pages = "221--228",
journal = "Current Opinion in Genetics and Development",
issn = "0959-437X",
publisher = "Elsevier Limited",
number = "3",

}

Chromosomal translocations and palindromic AT-rich repeats. / Kato, Takema; Kurahashi, Hiroki; Emanuel, Beverly S.

In: Current Opinion in Genetics and Development, Vol. 22, No. 3, 01.06.2012, p. 221-228.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Chromosomal translocations and palindromic AT-rich repeats

AU - Kato, Takema

AU - Kurahashi, Hiroki

AU - Emanuel, Beverly S.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84862504386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862504386&partnerID=8YFLogxK

U2 - 10.1016/j.gde.2012.02.004

DO - 10.1016/j.gde.2012.02.004

M3 - Review article

C2 - 22402448

AN - SCOPUS:84862504386

VL - 22

SP - 221

EP - 228

JO - Current Opinion in Genetics and Development

JF - Current Opinion in Genetics and Development

SN - 0959-437X

IS - 3

ER -