A biochemically defined system for coding joint formation in V(D)J recombination.

Molecular Cell
Haihui LuMichael R Lieber

Abstract

V(D)J recombination is one of the most complex DNA transactions in biology. The RAG complex makes double-stranded breaks adjacent to signal sequences and creates hairpin coding ends. Here, we find that the kinase activity of the Artemis:DNA-PKcs complex can be activated by hairpin DNA ends in cis, thereby allowing the hairpins to be nicked and then to undergo processing and joining by nonhomologous DNA end joining. Based on these insights, we have reconstituted many aspects of the antigen receptor diversification of V(D)J recombination by using 13 highly purified polypeptides, thereby permitting variable domain exon assembly by using this fully defined system in accord with the 12/23 rule for this process. The features of the recombination sites created by this system include all of the features observed in vivo (nucleolytic resection, P nucleotides, and N nucleotide addition), indicating that most, if not all, of the end modification enzymes have been identified.

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Citations

Dec 24, 2008·Molecular and Cellular Biology·Laurent MalivertJean-Pierre de Villartay
Jan 10, 2012·Annual Review of Immunology·Beth A Helmink, Barry P Sleckman
Jan 23, 2013·The Journal of Cell Biology·Jessica CottarelPatrick Calsou
Feb 2, 2010·Molecular Immunology·Anamika Bhattacharyya, Jessica M Jones
Mar 8, 2011·Mutation Research·Jessica A Neal, Katheryn Meek
May 18, 2017·Nature Reviews. Molecular Cell Biology·Howard H Y ChangMichael R Lieber
Dec 17, 2017·The Journal of Biological Chemistry·Nicholas R PannunzioMichael R Lieber
Feb 7, 2014·The Journal of Biological Chemistry·Sicong LiMichael R Lieber
Aug 16, 2015·The Journal of Biological Chemistry·Howard H Y ChangMichael R Lieber
Oct 21, 2020·Nature Reviews. Molecular Cell Biology·Bailin ZhaoMichael R Lieber
Aug 6, 2021·Molecular Cell·Amanda K ChaplinTom L Blundell

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