V(D)J recombination: how to tame a transposase

Immunological Reviews
Vicky L Brandt, D B Roth

Abstract

Since the discovery that the recombination-activating gene (RAG) proteins were capable of transposition in vitro, investigators have been trying to uncover instances of transposition in vivo and understand how this transposase has been harnessed to do useful work while being inhibited from causing deleterious chromosome rearrangements. How to preserve the capacity of the recombinase to promote a certain class of rearrangements while curtailing its ability to catalyze others is an interesting problem. In this review, we examine the progress that has been made toward understanding the regulatory mechanisms that prohibit transposition in order to formulate a model that takes into account the diverse observations that have been made over the last 15 years. First, we touch on the striking mechanistic similarities between transposition and V(D)J recombination and review evidence suggesting that the RAG proteins may be members of the retroviral integrase superfamily. We then dispense with an old theory that certain standard products of V(D)J recombination called signal joints protect against deleterious transposition events. Finally, we discuss the evidence that target capture could serve a regulatory role and close with an analysis o...Continue Reading

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Citations

Dec 24, 2004·Nature·Marjorie A Oettinger
Jul 21, 2007·Nature Immunology·Mila JankovicMichel C Nussenzweig
Nov 16, 2006·PLoS Biology·Jennifer E PoseyDavid B Roth
Jul 6, 2010·Seminars in Cancer Biology·Dale A RamsdenYeturu V R Reddy
Feb 24, 2009·Journal of Molecular Biology·Shuying ZhaoKarla K Rodgers
Dec 19, 2007·Molecular Microbiology·Richard J GradmanIgor Y Goryshin
Jan 30, 2007·Journal of Molecular Biology·Christian D AdamsWilliam S Reznikoff
Jan 24, 2015·Nature Communications·Jean-Marc NavarroBertrand Nadel
Jul 24, 2020·The Journal of Biological Chemistry·Gwendolyn Kaeser, Jerold Chun
Feb 6, 2020·Nature Structural & Molecular Biology·Xuemin ChenWei Yang

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