The major purpose of this project is to dissect the mechanism by which immunoglobulin and T-cell receptor genes are assembled into functional entities, and to study the regulation of this reaction. Several new results on this process, generally called V(D)J recombination, have been obtained. (1) Recombinants formed in fibroblast cell lines which express the RAG- 1 and RAG-2 genes rarely contain the added nucleotides which are characteristic of recombinants from lymphoid cells. The probable explanation is that fibroblasts lack the enzyme terminal deoxynucleotidyl transferase. (2) The recombinational defect of cell lines derived from mice with the scid mutation can be partly overcome by altering the cell culture conditions. The mutation is therefore leaky. (3) A molecular explanation for the preference of deletional over inversional D to J recombination at the immunoglobulin heavy-chain locus has emerged. The difference is due to several individually minor mutations in the upstream signal sequence associated with D regions.
| 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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