Journal Article

Involvement of V(D)J recombinase in the generation of intragenic deletions in the <i>Rit1/Bcl11b</i> tumor suppressor gene in γ-ray-induced thymic lymphomas and in normal thymus of the mouse

Jun Sakata, Jun Inoue, Hiroyuki Ohi, Hitomi Kosugi-Okano, Yukio Mishima, Katsuyoshi Hatakeyama, Ohtsura Niwa and Ryo Kominami

in Carcinogenesis

Volume 25, issue 6, pages 1069-1075
Published in print June 2004 | ISSN: 0143-3334
Published online June 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh094
Involvement of V(D)J recombinase in the generation of intragenic deletions in the Rit1/Bcl11b tumor suppressor gene in γ-ray-induced thymic lymphomas and in normal thymus of the mouse

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Mouse thymic lymphomas induced by γ-irradiation exhibited homozygous deletions of the Rit1/Bcl11b tumor suppressor gene on chromosome 12 at high frequencies. Internal deletions of one allele were frequently accompanied by loss of the other allele. In order to elucidate the mechanism of these internal deletions, the sites of breakage and rejoining were examined by PCR mapping and sequencing. The 5′ site of the deletions clustered within an ∼5 kb region of intron 1 and the 3′ site was confined to a site in intron 3. These sites contained P and/or N nucleotides and cryptic sequences recognizable by the RAG1/2 recombinase in the vicinity. This suggests that the Rit1 intragenic deletions were generated by endogenous illegitimate V(D)J recombinase activity and such aberrant recombination was also detected by nested PCR of DNA from the thymus of unirradiated mice but not of RAG2-deficient mice. A rough estimate indicated that there reside as many as 103–104 thymocytes having Rit1 deletions, assuming the presence of 108 thymocytes in the thymus of unirradiated mice. Moreover, the recombination frequency was not affected by γ-irradiation. These results show no effect of radiation on Rit1 mutations and suggest an indirect mechanism for its role in lymphomagenesis.

Keywords: DSBs, double-strand breaks; MNU, N-methyl-N-nitrosourea

Journal Article.  5145 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.