@article{oai:repo.qst.go.jp:00044524,
 author = {Tsuji, Hideo and Ishii-Ohba, Hiroko and Katsube, Takanori and Ukai, Hideki and Aizawa, Shirou and Doi, Masahiro and Hioki, Kyoji and Ogiu, Toshiaki and 辻 秀雄 and 石井 洋子 and 勝部 孝則 and 鵜飼 英樹 and 相澤 志郎 and 土居 雅広 and 荻生 俊昭},
 journal = {Cancer Research},
 month = {Dec},
 note = {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.},
 pages = {8882--8890},
 title = {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},
 volume = {64},
 year = {2004}
}