Requirement for ubiquitin conjugation and 26S proteasome activity at an early stage in V(D)J recombination.

Molecular Immunology
Anamika Bhattacharyya, Jessica M Jones

Abstract

V(D)J recombination, the process that rearranges gene segments to assemble mature antigen receptor genes, relies on a recombinase comprising the RAG1 and RAG2 proteins. RAG1 is a multi-functional enzyme including DNA binding and cleavage as well as ubiquitin ligase activities, all of which appear to contribute to its role in recombination. Here we demonstrate that components of the ubiquitin conjugation machinery and the 26S proteasome are required for an early step in V(D)J recombination. Inhibitors of the 26S proteasome and ubiquitin activating enzyme (E1) blocked both chromosomal and extra-chromosomal recombination when added 1h following transfection/induction, but they had no effect when added 16 h later. There was no effect on expression of RAG1, and recombination did not require transit through the cell cycle, confirming that inhibition was not due to an indirect effect on cell cycle arrest or protein expression. Experiments in which RAG1 translation was blocked with cyclohexamide after 16 h of expression indicated that many active recombination complexes were formed within this window, although recombination products continued to accumulate for 48 h. These data suggest that ubiquitin-dependent degradation is an early st...Continue Reading

References

Dec 22, 1989·Cell·D G SchatzD Baltimore
Apr 14, 1983·Nature·S Tonegawa
Mar 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·A HershkoH Heller
Oct 1, 1995·Genes & Development·D A Ramsden, M Gellert
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·W C Lin, S Desiderio
Dec 11, 1993·Nucleic Acids Research·M J SadofskyM Gellert
Apr 1, 1996·The Journal of Experimental Medicine·U GrawunderF Melchers
Dec 6, 1996·Science·R W KingM W Kirschner
Jun 8, 2001·Annual Review of Biochemistry·C M Pickart
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·J M Jones, M Gellert
Jun 5, 2002·Annual Review of Biochemistry·Martin Gellert
Mar 12, 2003·Genes & Development·Vyacheslav YurchenkoMoshe Sadofsky
Dec 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jessica M Jones, Martin Gellert
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·F Betul GulogluChristopher A J Roman
Nov 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Santiago Ramón-MaiquesWei Yang
Nov 23, 2007·Nature·Adam G W MatthewsMarjorie A Oettinger
Dec 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carrie SimkusJessica M Jones
Dec 7, 2007·Nature Cell Biology·Tatjana ShmidtMichael Bader
Aug 30, 2008·Molecular Cell·Haihui LuMichael R Lieber
Jan 3, 2009·Molecular Immunology·Carrie SimkusJessica M Jones

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