Our earlier work on antigen receptor gene rearrangement (V(D)J recombination) described one type of broken DNA molecules that were plausible intermediates in this process. These molecules, seen at the T cell receptor delta locus (TCR), had only the free end containing the recombination signal sequence. We have now also been able to find broken molecules with the end of the coding sequence, but only in DNA from mice with the scid mutation, which interferes with the joining of these ends. The coding ends are found to have an abnormal structure: the two DNA strands are linked to each other in a hairpin configuration.The presence of hairpins offers a good explanation for the observation, in immunoglobulin and T cell receptor coding junctions, of self- complementary sequences formed during recombination. If a hairpin structure is nicked off-center, a self- complementary insertion will naturally result. These results strengthen the evidence for a breakage-reunion model of V(D)J recombination, but also indicate that the process must be different from earlier examples of this type.
| Jones, Jessica M; Gellert, Martin (2004) The taming of a transposon: V(D)J recombination and the immune system. Immunol Rev 200:233-48 |
| Modesti, Mauro; Junop, Murray S; Ghirlando, Rodolfo et al. (2003) Tetramerization and DNA ligase IV interaction of the DNA double-strand break repair protein XRCC4 are mutually exclusive. J Mol Biol 334:215-28 |
| Jones, Jessica M; Gellert, Martin (2003) Autoubiquitylation of the V(D)J recombinase protein RAG1. Proc Natl Acad Sci U S A 100:15446-51 |
| Paull, T T; Cortez, D; Bowers, B et al. (2001) Direct DNA binding by Brca1. Proc Natl Acad Sci U S A 98:6086-91 |
| Jones, J M; Gellert, M (2001) Intermediates in V(D)J recombination: a stable RAG1/2 complex sequesters cleaved RSS ends. Proc Natl Acad Sci U S A 98:12926-31 |
| Jones, J M; Gellert, M; Yang, W (2001) A Ku bridge over broken DNA. Structure 9:881-4 |
| Paull, T T; Rogakou, E P; Yamazaki, V et al. (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10:886-95 |
| Paull, T T; Gellert, M (2000) A mechanistic basis for Mre11-directed DNA joining at microhomologies. Proc Natl Acad Sci U S A 97:6409-14 |
| Roth, D B; Gellert, M (2000) New guardians of the genome. Nature 404:823-5 |
| Junop, M S; Modesti, M; Guarne, A et al. (2000) Crystal structure of the Xrcc4 DNA repair protein and implications for end joining. EMBO J 19:5962-70 |
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