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DNA bending in the synaptic complex in V(D)J recombination: turning an ancestral transpososome upside down

DISCOVERIES (ISSN 2359-7232), 2014, January-March

CITATION:

Ciubotaru M, Surleac M, Mihaela G. Musat MG, Rusu AM, Ionita E, Albu PCC. DNA bending in the synaptic complex in V(D)J recombination; turning an ancestral transpososome upside down. Discoveries 2014, Jan-Mar; 2(1): e13. DOI: 10.15190/d.2014.5;

Submitted: March 17, 2014; Published online:March 29, 2014

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DNA bending in the synaptic complex in V(D)J recombination: turning an ancestral transpososome upside down


(1,2,*), (3), (2) (2), (2) and (2)


Affiliation:
(1) Department of Immunobiology, Yale University School of Medicine, 300 Cedar St., TAC S620, New Haven, CT 06511, USA. (2) National Institute for Physics and Nuclear Engineering Horia Hulubei, Department of Life and Environmental Physics, Atomistilor Str., 077125, Bucharest-Magurele, Romania. (3) Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry of the Romanian Academy, Splaiul Independentei 296, 060031, Bucharest, Romania

*Correspondence should be addressed to: Mihai Ciubotaru, PhD, Department of Immunobiology, Yale University School of Medicine, 300 Cedar St., TAC S620, New Haven, CT 06511, USA, Phone: 011-1-203-785-3247; Fax: 011-1-203-785-3855; Email: mihai.ciubotaru@yale.edu


Abstract


In all jawed vertebrates RAG (recombination activating gene) recombinase orchestrates V(D)J recombination in B and T lymphocyte precursors, assembling the V, D and J germline gene segments into continuous functional entities which encode the variable regions of their immune receptors. V(D)J recombination is the process by which most of the diversity of our specific immune receptors is acquired and is thought to have originated by domestication of a transposon in the genome of a vertebrate. Although RAG reaction mechanism resembles that of some insect mobile element transposases and RAG itself can inefficiently perform intra and intermolecular integration into target DNA, for it, inside the nuclei of the developing lymphocytes transposition is extremely rare and is kept under proper surveillance. Our review may help understanding how RAG synaptic complex organization prevents deleterious transposition. The phosphoryl transfer reaction mechanism of RNAseH-like fold DDE motif enzymes, including RAG, is discussed accentuating the peculiarities described for various transposases from the light of their available high resolution structures (Tn5, Mu, Mos1 and Hermes). Contrasting the structural 3D organization of DNA in these transpososomes with that of the RSSs (recombination signal sequences)-DNA in RAG paired complex (PC) allows us to propose several clues for how evolutionarily RAG may have become “specialized” in recombination versus transposition.

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