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 language | English |
|---|---|
| Article number | 18 |
| Journal | Molecular Cytogenetics |
| Volume | 4 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 14-09-2011 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Genetics
- Genetics(clinical)
- Biochemistry, medical
Cite this
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DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation. / Kato, Takema; Inagaki, Hidehito; Tong, Maoqing; Kogo, Hiroshi; Ohye, Tamae; Yamada, Kouji; Tsutsumi, Makiko; Emanuel, Beverly S.; Kurahashi, Hiroki.
In: Molecular Cytogenetics, Vol. 4, No. 1, 18, 14.09.2011.Research output: Contribution to journal › Article
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.
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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 -