Intermediates in V(D)J recombination: a stable RAG1/2 complex sequesters cleaved RSS ends

Proceedings of the National Academy of Sciences of the United States of America
J M Jones, M Gellert

Abstract

Rearrangement of gene segments to generate antigen receptor coding regions depends on the RAG1/2 recombinase, which assembles a synaptic complex between two DNA signal sequences and then cleaves the DNA directly adjacent to the paired signals. After coupled cleavage of complementary signal sequences, virtually all of the cleaved signal ends remained associated with RAG1/2 in stable complexes. These signal end complexes were distinct from various precleavage RAG1/2 signal complexes in that they were resistant to treatment with heparin. A mammalian joining apparatus consisting of purified Ku70/86, XRCC4, and DNA ligase IV proteins was sufficient to join deproteinized cleaved ends, but retention of signal sequences within the signal end complex blocked access to the DNA ends and prevented their joining by these proteins. Sequestration of cleaved ends within the signal end complex would account for the persistence of these ends in the cell after cleavage and may explain why they do not normally activate the DNA-damage-dependent cell cycle checkpoint.

References

Jan 1, 1992·Current Topics in Microbiology and Immunology·D B RothM Gellert
Oct 25, 1991·Nucleic Acids Research·S Paillard, F Strauss
Apr 14, 1983·Nature·S Tonegawa
Oct 1, 1995·Genes & Development·D A Ramsden, M Gellert
Jun 1, 1995·Immunology Today·W C Lin, S Desiderio
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D B RothM Gellert
Feb 28, 1997·The Journal of Biological Chemistry·T M Bliss, D P Lane
Jan 1, 1997·Advances in Immunology·M Gellert
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·R B CaryD J Chen
May 15, 1997·The EMBO Journal·D C van GentM Gellert
Jul 31, 1997·Nature·D A RamsdenM Gellert
Aug 1, 1997·Current Biology : CB·S E CritchlowS P Jackson
Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Dec 16, 1998·Immunological Reviews·M S KrangelX P Zhong
Mar 19, 1999·Molecular and Cellular Biology·S B SteenD B Roth
Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Feb 26, 2000·Annual Review of Genetics·D Zickler, N Kleckner
Apr 11, 2000·Molecular and Cellular Biology·S A Nick McElhinnyD A Ramsden
Jun 16, 2000·The Journal of Biological Chemistry·L ChenA E Tomkinson
Jun 28, 2000·Proceedings of the National Academy of Sciences of the United States of America·B P SleckmanF W Alt
Dec 9, 2000·Science·H T ChenA Nussenzweig
Apr 3, 2001·The Journal of Experimental Medicine·M S Krangel

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Citations

Apr 1, 2009·Archivum Immunologiae Et Therapiae Experimentalis·Jessica M Jones, Carrie Simkus
Mar 1, 2002·Current Opinion in Immunology·Vicky L Brandt, David B Roth
Dec 11, 2002·European Journal of Biochemistry·Alexei V Cherepanov, Simon de Vries
Jul 30, 2002·The EMBO Journal·Jessica M Jones, Martin Gellert
Aug 26, 2004·Nucleic Acids Research·Sadiqur R TalukderYoshiko Akamatsu
Feb 19, 2008·Nucleic Acids Research·Prafulla RavalPatrick C Swanson
Jan 10, 2012·Nucleic Acids Research·Sunetra RoyKatheryn Meek
Sep 21, 2002·Molecular and Cellular Biology·Fumikiyo NagawaHitoshi Sakano
Apr 15, 2004·Molecular and Cellular Biology·Tadashi NishiharaHitoshi Sakano
Feb 2, 2006·Molecular and Cellular Biology·Monalisa ChatterjiDavid G Schatz
Dec 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jessica M Jones, Martin Gellert
Aug 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Aurélie MousnierCatherine Dargemont
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Meni MelekMartin Gellert
Jan 10, 2012·Annual Review of Immunology·Beth A Helmink, Barry P Sleckman
Aug 23, 2011·Annual Review of Genetics·David G Schatz, Patrick C Swanson
Jul 10, 2004·Immunological Reviews·Patrick C Swanson
Jul 10, 2004·Immunological Reviews·Françoise Le DeistJean-Pierre de Villartay
Jul 10, 2004·Immunological Reviews·Monalisa ChatterjiDavid G Schatz
Jul 10, 2004·Immunological Reviews·Vicky L Brandt, David B Roth
Jul 10, 2004·Immunological Reviews·Jessica M Jones, Martin Gellert
Nov 4, 2004·Seminars in Immunology·David G Schatz
Feb 2, 2010·Molecular Immunology·Anamika Bhattacharyya, Jessica M Jones
Apr 8, 2014·Cell Reports·Amjad AskaryMichael R Lieber
Oct 11, 2003·Molecular Cell·Anne E ClatworthyMarjorie A Oettinger
Aug 30, 2008·Molecular Cell·Haihui LuMichael R Lieber
Jan 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Eric J GapudBarry P Sleckman
Jul 6, 2014·The Journal of Allergy and Clinical Immunology·Hassan AbolhassaniLennart Hammarström
Sep 17, 2003·Nature Reviews. Immunology·David B Roth
Feb 25, 2015·Nature·Min-Sung KimMartin Gellert
Jan 31, 2004·Current Opinion in Allergy and Clinical Immunology·Jean-Pierre de Villartay

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