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Involvement of Illegitimate V(D)J Recombination or Microhomology-Mediated Nonhomologous End-Joining in the Formation of Intragenic Deletions of the Notch1 Gene in Mouse Thymic Lymphomas
https://repo.qst.go.jp/records/44524
https://repo.qst.go.jp/records/4452429d136b9-9172-4aa6-acf6-0149b12086a7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-08-03 | |||||
| タイトル | ||||||
| タイトル | Involvement of Illegitimate V(D)J Recombination or Microhomology-Mediated Nonhomologous End-Joining in the Formation of Intragenic Deletions of the Notch1 Gene in Mouse Thymic Lymphomas | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Tsuji, Hideo
× Tsuji, Hideo× Ishii-Ohba, Hiroko× Katsube, Takanori× Ukai, Hideki× Aizawa, Shirou× Doi, Masahiro× Hioki, Kyoji× Ogiu, Toshiaki× 辻 秀雄× 石井 洋子× 勝部 孝則× 鵜飼 英樹× 相澤 志郎× 土居 雅広× 荻生 俊昭 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Deregulated V(D)J recombination-mediated chromosomal rearrangements are implicated in the etiology of B- and T-cell lymphomagenesis. We describe here three pathways for the formation of the 5' deletions of Notch1 gene in thymic lymphomas of wild-type or V(D)J recombination-defective scid mice. A pair of recombination signal sequence -like sequences composed of heptamer-like and nonamer-like motifs separated by 12- or 23-bp spacers (12- or 23-recombination signal sequence) were present in the vicinity of the deletion breakpoints in wild-type thymic lymphomas, accompanied by palindromic or nontemplated nucleotides at the junctions. In scid thymic lymphomas the deletions at the recombination signal sequence-like sequences occurred at a significantly lower frequency than in wild-type mice, whereas the deletions did not occur in Rag2-/- thymocytes. These results show that the 5' deletions are formed by Rag-mediated V(D)J recombination machinery at cryptic recombination signal sequences in the Notch1 locus. In contrast, one third of the deletions in radiation-induced scid thymic lymphomas had microhomology at both ends, indicating that in the absence of DNA-dependent protein kinase-dependent nonhomologous end-joining, the microhomology-mediated nonhomologous endjoining pathway functions as a main mechanism to produce deletions. Furthermore the deletions were induced via a coupled pathway between Rag-mediated cleavage at cryptic recombination signal sequence and micronomology-mediated end-joining in radiation-induced scid thymic lymphomas. As the deletions at cryptic recombination signal sequence occur spontaneously, microhomology-mediated pathways might participate mainly in in radiation-induced lymphomagenesis. Recombination signal sequence-mediated deletions were present clonally in thymocyte population, suggesting that thymocytes with a 5'deletion of the Notch1 gene have a growth advantage and are involved in lymphomagenesis. | |||||
| 書誌情報 |
Cancer Research 巻 64, p. 8882-8890, 発行日 2004-12 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0008-5472 | |||||
