Mechanisms of Genomic Instabilities Underlying Two Common Fragile-Site-Associated Loci, PARK2 and DMD, in Germ Cell and Cancer Cell Lines
Identifieur interne : 000B74 ( Ncbi/Curation ); précédent : 000B73; suivant : 000B75Mechanisms of Genomic Instabilities Underlying Two Common Fragile-Site-Associated Loci, PARK2 and DMD, in Germ Cell and Cancer Cell Lines
Auteurs : Jun Mitsui [Japon] ; Yuji Takahashi [Japon] ; Jun Goto [Japon] ; Hiroyuki Tomiyama [Japon] ; Shunpei Ishikawa [Japon] ; Hiroyo Yoshino [Japon] ; Narihiro Minami [Japon] ; David I. Smith [États-Unis] ; Suzanne Lesage [France] ; Hiroyuki Aburatani [Japon] ; Ichizo Nishino [Japon] ; Alexis Brice [France] ; Nobutaka Hattori [Japon] ; Shoji Tsuji [Japon]Source :
- American Journal of Human Genetics [ 0002-9297 ] ; 2010.
Abstract
Common fragile sites (CFSs) are specific chromosome regions that exhibit an increased frequency of breaks when cells are exposed to a DNA-replication inhibitor such as aphidicolin.
Url:
DOI: 10.1016/j.ajhg.2010.06.006
PubMed: 20598272
PubMed Central: 2896763
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, in Germ Cell and Cancer Cell Lines</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mechanisms of Genomic Instabilities Underlying Two Common Fragile-Site-Associated Loci, <italic>PARK2</italic>
and <italic>DMD</italic>
, in Germ Cell and Cancer Cell Lines</title>
<author><name sortKey="Mitsui, Jun" sort="Mitsui, Jun" uniqKey="Mitsui J" first="Jun" last="Mitsui">Jun Mitsui</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
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<author><name sortKey="Takahashi, Yuji" sort="Takahashi, Yuji" uniqKey="Takahashi Y" first="Yuji" last="Takahashi">Yuji Takahashi</name>
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<country xml:lang="fr">Japon</country>
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<author><name sortKey="Goto, Jun" sort="Goto, Jun" uniqKey="Goto J" first="Jun" last="Goto">Jun Goto</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
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<author><name sortKey="Ishikawa, Shunpei" sort="Ishikawa, Shunpei" uniqKey="Ishikawa S" first="Shunpei" last="Ishikawa">Shunpei Ishikawa</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
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<author><name sortKey="Yoshino, Hiroyo" sort="Yoshino, Hiroyo" uniqKey="Yoshino H" first="Hiroyo" last="Yoshino">Hiroyo Yoshino</name>
<affiliation wicri:level="1"><nlm:aff id="aff4">Research Institute for Diseases of Old Ages, Juntendo University School of Medicine, Tokyo 113-8421, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Research Institute for Diseases of Old Ages, Juntendo University School of Medicine, Tokyo 113-8421</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Minami, Narihiro" sort="Minami, Narihiro" uniqKey="Minami N" first="Narihiro" last="Minami">Narihiro Minami</name>
<affiliation wicri:level="1"><nlm:aff id="aff5">Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, David I" sort="Smith, David I" uniqKey="Smith D" first="David I." last="Smith">David I. Smith</name>
<affiliation wicri:level="2"><nlm:aff id="aff6">Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55902</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
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<author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name>
<affiliation wicri:level="1"><nlm:aff id="aff7">CRicm, University Pierre et Marie Curie, INSERM, UMR_S975, CNRS UMR 7225, Hospital Pitié-Salpêtrière, 75651 Paris, CEDEX 13, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CRicm, University Pierre et Marie Curie, INSERM, UMR_S975, CNRS UMR 7225, Hospital Pitié-Salpêtrière, 75651 Paris, CEDEX 13</wicri:regionArea>
<wicri:noRegion>CEDEX 13</wicri:noRegion>
<wicri:noRegion>CEDEX 13</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Aburatani, Hiroyuki" sort="Aburatani, Hiroyuki" uniqKey="Aburatani H" first="Hiroyuki" last="Aburatani">Hiroyuki Aburatani</name>
<affiliation wicri:level="1"><nlm:aff id="aff8">Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
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<author><name sortKey="Nishino, Ichizo" sort="Nishino, Ichizo" uniqKey="Nishino I" first="Ichizo" last="Nishino">Ichizo Nishino</name>
<affiliation wicri:level="1"><nlm:aff id="aff5">Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
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<author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name>
<affiliation wicri:level="1"><nlm:aff id="aff7">CRicm, University Pierre et Marie Curie, INSERM, UMR_S975, CNRS UMR 7225, Hospital Pitié-Salpêtrière, 75651 Paris, CEDEX 13, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CRicm, University Pierre et Marie Curie, INSERM, UMR_S975, CNRS UMR 7225, Hospital Pitié-Salpêtrière, 75651 Paris, CEDEX 13</wicri:regionArea>
<wicri:noRegion>CEDEX 13</wicri:noRegion>
<wicri:noRegion>CEDEX 13</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421</wicri:regionArea>
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</placeName>
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</author>
<author><name sortKey="Tsuji, Shoji" sort="Tsuji, Shoji" uniqKey="Tsuji S" first="Shoji" last="Tsuji">Shoji Tsuji</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
</placeName>
</affiliation>
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<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="eISSN">1537-6605</idno>
<imprint><date when="2010">2010</date>
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<front><div type="abstract" xml:lang="en"><p>Common fragile sites (CFSs) are specific chromosome regions that exhibit an increased frequency of breaks when cells are exposed to a DNA-replication inhibitor such as aphidicolin. <italic>PARK2</italic>
and <italic>DMD,</italic>
the causative genes for autosomal-recessive juvenile Parkinsonism and Duchenne and Becker muscular dystrophy, respectively, are two very large genes that are located within aphidicolin-induced CFSs. Gross rearrangements within these two genes are frequently observed as the causative mutations for these diseases, and similar alterations within the large fragile sites that surround these genes are frequently observed in cancer cells. To elucidate the molecular mechanisms underlying this fragility, we performed a custom-designed high-density comparative genomic hybridization analysis to determine the junction sequences of approximately 500 breakpoints in germ cell lines and cancer cell lines involving <italic>PARK2</italic>
or <italic>DMD</italic>
. The sequence signatures where these breakpoints occur share some similar features both in germ cell lines and in cancer cell lines. Detailed analyses of these structures revealed that microhomologies are predominantly involved in rearrangement processes. Furthermore, breakpoint-clustering regions coincide with the latest-replicating region and with large nuclear-lamina-associated domains and are flanked by the highest-flexibility peaks and R/G band boundaries, suggesting that factors affecting replication timing collectively contribute to the vulnerability for rearrangement in both germ cell and somatic cell lines.</p>
</div>
</front>
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