DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation

Takema Kato, Hidehito Inagaki, Maoqing Tong, Hiroshi Kogo, Tamae Ohye, Kouji Yamada, Makiko Tsutsumi, Beverly S. Emanuel, Hiroki Kurahashi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background. Cumulative evidence suggests that DNA secondary structures impact DNA replication, transcription and genomic rearrangements. One of the best studied examples is the recurrent constitutional t(11;22) in humans that is mediated by potentially cruciform-forming sequences at the breakpoints, palindromic AT-rich repeats (PATRRs). We previously demonstrated that polymorphisms of PATRR sequences affect the frequency of de novo t(11;22)s in sperm samples from normal healthy males. These studies were designed to determine whether PATRR polymorphisms affect DNA secondary structure, thus leading to variation in translocation frequency. Methods. We studied the potential for DNA cruciform formation for several PATRR11 polymorphic alleles using mobility shift analysis in gel electrophoresis as well as by direct visualization of the DNA by atomic force microscopy. The structural data for various alleles were compared with the frequency of de novo t(11;22)s the allele produced. Results. The data indicate that the propensity for DNA cruciform structure of each polymorphic allele correlates with the frequency of de novo t(11;22)s produced (r = 0.77, P = 0.01). Conclusions. Although indirect, our results strongly suggest that the PATRR adopts unstable cruciform structures during spermatogenesis that act as translocation hotspots in humans.

Original languageEnglish
Article number18
JournalMolecular Cytogenetics
Volume4
Issue number1
DOIs
Publication statusPublished - 14-09-2011

Fingerprint

Alleles
Cruciform DNA
DNA
AT Rich Sequence
Polymorphism
Atomic Force Microscopy
Electrophoretic Mobility Shift Assay
Spermatogenesis
DNA Replication
Electrophoresis
Spermatozoa
Transcription
Atomic force microscopy
Visualization
Gels

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Biochemistry, medical

Cite this

@article{88f184c03d4e4ade84b229a1735dcd60,
title = "DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation",
abstract = "Background. Cumulative evidence suggests that DNA secondary structures impact DNA replication, transcription and genomic rearrangements. One of the best studied examples is the recurrent constitutional t(11;22) in humans that is mediated by potentially cruciform-forming sequences at the breakpoints, palindromic AT-rich repeats (PATRRs). We previously demonstrated that polymorphisms of PATRR sequences affect the frequency of de novo t(11;22)s in sperm samples from normal healthy males. These studies were designed to determine whether PATRR polymorphisms affect DNA secondary structure, thus leading to variation in translocation frequency. Methods. We studied the potential for DNA cruciform formation for several PATRR11 polymorphic alleles using mobility shift analysis in gel electrophoresis as well as by direct visualization of the DNA by atomic force microscopy. The structural data for various alleles were compared with the frequency of de novo t(11;22)s the allele produced. Results. The data indicate that the propensity for DNA cruciform structure of each polymorphic allele correlates with the frequency of de novo t(11;22)s produced (r = 0.77, P = 0.01). Conclusions. Although indirect, our results strongly suggest that the PATRR adopts unstable cruciform structures during spermatogenesis that act as translocation hotspots in humans.",
author = "Takema Kato and Hidehito Inagaki and Maoqing Tong and Hiroshi Kogo and Tamae Ohye and Kouji Yamada and Makiko Tsutsumi and Emanuel, {Beverly S.} and Hiroki Kurahashi",
year = "2011",
month = "9",
day = "14",
doi = "10.1186/1755-8166-4-18",
language = "English",
volume = "4",
journal = "Molecular Cytogenetics",
issn = "1755-8166",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation

AU - Kato, Takema

AU - Inagaki, Hidehito

AU - Tong, Maoqing

AU - Kogo, Hiroshi

AU - Ohye, Tamae

AU - Yamada, Kouji

AU - Tsutsumi, Makiko

AU - Emanuel, Beverly S.

AU - Kurahashi, Hiroki

PY - 2011/9/14

Y1 - 2011/9/14

N2 - Background. Cumulative evidence suggests that DNA secondary structures impact DNA replication, transcription and genomic rearrangements. One of the best studied examples is the recurrent constitutional t(11;22) in humans that is mediated by potentially cruciform-forming sequences at the breakpoints, palindromic AT-rich repeats (PATRRs). We previously demonstrated that polymorphisms of PATRR sequences affect the frequency of de novo t(11;22)s in sperm samples from normal healthy males. These studies were designed to determine whether PATRR polymorphisms affect DNA secondary structure, thus leading to variation in translocation frequency. Methods. We studied the potential for DNA cruciform formation for several PATRR11 polymorphic alleles using mobility shift analysis in gel electrophoresis as well as by direct visualization of the DNA by atomic force microscopy. The structural data for various alleles were compared with the frequency of de novo t(11;22)s the allele produced. Results. The data indicate that the propensity for DNA cruciform structure of each polymorphic allele correlates with the frequency of de novo t(11;22)s produced (r = 0.77, P = 0.01). Conclusions. Although indirect, our results strongly suggest that the PATRR adopts unstable cruciform structures during spermatogenesis that act as translocation hotspots in humans.

AB - Background. Cumulative evidence suggests that DNA secondary structures impact DNA replication, transcription and genomic rearrangements. One of the best studied examples is the recurrent constitutional t(11;22) in humans that is mediated by potentially cruciform-forming sequences at the breakpoints, palindromic AT-rich repeats (PATRRs). We previously demonstrated that polymorphisms of PATRR sequences affect the frequency of de novo t(11;22)s in sperm samples from normal healthy males. These studies were designed to determine whether PATRR polymorphisms affect DNA secondary structure, thus leading to variation in translocation frequency. Methods. We studied the potential for DNA cruciform formation for several PATRR11 polymorphic alleles using mobility shift analysis in gel electrophoresis as well as by direct visualization of the DNA by atomic force microscopy. The structural data for various alleles were compared with the frequency of de novo t(11;22)s the allele produced. Results. The data indicate that the propensity for DNA cruciform structure of each polymorphic allele correlates with the frequency of de novo t(11;22)s produced (r = 0.77, P = 0.01). Conclusions. Although indirect, our results strongly suggest that the PATRR adopts unstable cruciform structures during spermatogenesis that act as translocation hotspots in humans.

UR - http://www.scopus.com/inward/record.url?scp=80052588393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052588393&partnerID=8YFLogxK

U2 - 10.1186/1755-8166-4-18

DO - 10.1186/1755-8166-4-18

M3 - Article

C2 - 21899780

AN - SCOPUS:80052588393

VL - 4

JO - Molecular Cytogenetics

JF - Molecular Cytogenetics

SN - 1755-8166

IS - 1

M1 - 18

ER -