Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats

Hiroshi Kogo, Hidehito Inagaki, Tamae Oe, Takema Kato, Beverly S. Emanuel, Hiroki Kurahashi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 (∼600bp), PATRR11 (∼450bp) and PATRR17 (∼190bp). 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.

Original languageEnglish
Pages (from-to)1198-1208
Number of pages11
JournalNucleic Acids Research
Volume35
Issue number4
DOIs
Publication statusPublished - 01-02-2007

Fingerprint

Genomic Instability
Endonucleases
Osmolar Concentration
Escherichia coli
DNA
Incidence
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

@article{6ee009df8a4e4569a552c9e41e1595f2,
title = "Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats",
abstract = "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 (∼600bp), PATRR11 (∼450bp) and PATRR17 (∼190bp). 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.",
author = "Hiroshi Kogo and Hidehito Inagaki and Tamae Oe and Takema Kato and Emanuel, {Beverly S.} and Hiroki Kurahashi",
year = "2007",
month = "2",
day = "1",
doi = "10.1093/nar/gkm036",
language = "English",
volume = "35",
pages = "1198--1208",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "4",

}

Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats. / Kogo, Hiroshi; Inagaki, Hidehito; Oe, Tamae; Kato, Takema; Emanuel, Beverly S.; Kurahashi, Hiroki.

In: Nucleic Acids Research, Vol. 35, No. 4, 01.02.2007, p. 1198-1208.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats

AU - Kogo, Hiroshi

AU - Inagaki, Hidehito

AU - Oe, Tamae

AU - Kato, Takema

AU - Emanuel, Beverly S.

AU - Kurahashi, Hiroki

PY - 2007/2/1

Y1 - 2007/2/1

N2 - 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 (∼600bp), PATRR11 (∼450bp) and PATRR17 (∼190bp). 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.

AB - 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 (∼600bp), PATRR11 (∼450bp) and PATRR17 (∼190bp). 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.

UR - http://www.scopus.com/inward/record.url?scp=34047101901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047101901&partnerID=8YFLogxK

U2 - 10.1093/nar/gkm036

DO - 10.1093/nar/gkm036

M3 - Article

VL - 35

SP - 1198

EP - 1208

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 4

ER -