Two new and unusual products of V(D)J recombination in lymphoid cells have been identified. Normal recombination joins the two signal sequences that identify the rearrangement site and, in the complementary reaction, joins the fragments of coding sequences that flank the signals. In extrachromosomal plasmid substrates, these products are found, but there is also a class of """"""""hybrid joints"""""""" that link one signal to the coding flank of its partner signal. A second class of """"""""open and shut"""""""" events rejoins each signal to its own flank, and is identifiable because of nucleotides lost and/or added at the joint. Both these products supply evidence that DNA strand alignment is not precisely specified in V(D)J recombination. A specific defect of V(D)J recombination has been identified in lymphoid cell lines derived from mice with the severe combined immune deficiency (scid) mutation. In extrachromosomal substrates, these cells make signal joints (though with greater imprecision than normal) but are unable to make coding joints. This failure appears sufficient to explain the absence of functional B and T cells in scid mice.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
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
Melek, M; Gellert, M (2000) RAG1/2-mediated resolution of transposition intermediates: two pathways and possible consequences. Cell 101:625-33
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

Showing the most recent 10 out of 11 publications