The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination

Spanopoulou, Eugenia; Zaitseva, Florina; Wang, Fu-Hou; Santagata, Sandro; Baltimore, David; Panayotou, George

doi:10.1016/s0092-8674(00)81344-6

Cited by 225DNA Repair MechanismsT-cell and B-cell ImmunologyGenomics and Chromatin Dynamics

The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination

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Spanopoulou, Eugenia, Zaitseva, Florina, Wang, Fu-Hou, Santagata, Sandro, Baltimore, David, Panayotou, George·1996·Cell

DOI 10.1016/s0092-8674(00)81344-6

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Abstract

The V(D)J recombinase subunits Rag-1 and Rag-2 mediate assembly of antigen receptor gene segments. We studied the mechanisms of DNA recognition by Rag-1/Rag-2 using surface plasmon resonance. The critical step for signal recognition is binding of Rag-1 to the nonamer. This is achieved by a region of Rag-1 homologous to the DNA-binding domain of the Hin family of bacterial invertases and to homeodomain proteins. Strikingly, the Hin homeodomain can functionally substitute for the Rag-1 homologous region. Rag-1 also interacts with the heptamer but with low affinity. Rag-2 shows no direct binding to DNA. Once the Rag-1/Rag-2 complex is engaged on the DNA, subsequent cleavage is directed by the heptamer sequence. This order of events remarkably parallels mechanisms that mediate transposition in bacteria and nematodes.

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The RAG1 core is split into separate exons at the amino acid position corresponding to position 460 in the human RAG1 gene.
“As a result, the RAG1 core is split into separate exons at the aa position that corresponds to position 460 in the human RAG1gene [29,34,38].”
From RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons (2005) · cites this paper as [29]
In teleosts, the RAG1 gene is divided into exons by either one or two introns.
“This is consistent with the observation that in teleosts, (bony fish) the RAG1 gene is divided into exons by either one or two introns.”
From RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons (2005) · cites this paper as [29]

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Authors: Spanopoulou, E., Zaitseva, F., Wang, F.-H., Santagata, S., Baltimore, D., & Panayotou, G.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Massachusetts Institute of Technology (US)
Ludwig Cancer Research (GB)
Corresponding author: Spanopoulou, Eugenia
ORCID: Santagata, Sandro
Baltimore, David
Panayotou, George
Venue: Cell
Publisher: Elsevier BV
Published: 1996-10
Volume: 87
Issue: 2
Pages: 263-276
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)81344-6
OpenAlex: W2067022774
Cited by: 225
References: 62
Citations by year: 2024: 3 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 4
FWCI: 8.83
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6133 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: RAG1, RAG2, V(D)J recombination, homeodomain, DNA-binding domain, heptamer, transposon transposition, bacterial recombination, surface plasmon resonance
MeSH terms: Amino Acid Sequence, Binding Sites, DNA Transposable Elements, DNA Nucleotidyltransferases, DNA-Binding Proteins, Biological Evolution, Genes, Homeobox, Genes, Immunoglobulin, Humans, Molecular Sequence Data, Proteins, Recombinant Fusion Proteins, Recombinant Proteins, Recombination, Genetic, Structure-Activity Relationship, Transfection, Homeodomain Proteins

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The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination

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