Assembly of a 12/23 paired signal complex: a critical control point in V(D)J recombination

Kevin Hiom, Martin Gellert (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    195 Citations (Scopus)

    Abstract

    The 12/23 rule requires that V(D)J recombination only occurs between recombination signals with 12 and 23 base pair spacers. We show that the 12/23 rule is established prior to DNA cleavage, by the formation of a synaptic complex containing both 12-spacer and 23-spacer signals. The RAG1 and RAG2 proteins, as well as the DNA bending protein HMG1, are needed for efficient formation of this complex. We show further that the synaptic complex is the functional complex for coupled cleavage. After cleavage, all four broken DNA ends remain associated with the RAG proteins in a postcleavage synaptic complex, whose existence helps to explain the known role of RAG1 and RAG2 in the subsequent end-joining events that complete V(D)J recombination.

    Original languageEnglish
    Pages (from-to)1011-1019
    Number of pages9
    JournalMolecular Cell
    Volume1
    Issue number7
    DOIs
    Publication statusPublished - Jun 1998

    Fingerprint

    V(D)J Recombination
    HMGB1 Protein
    DNA Cleavage
    Proteins
    DNA
    Base Pairing
    Genetic Recombination

    Keywords

    • Base composition
    • DNA
    • DNA-binding proteins
    • Gene rearrangement
    • Genes, Immunoglobulin
    • High mobility group proteins
    • Homeodomain proteins
    • Immunoglobulin J-chains
    • Immunoglobulin variable Region
    • Mutation
    • Protein binding
    • Recombination, Genetic

    Cite this

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    title = "Assembly of a 12/23 paired signal complex: a critical control point in V(D)J recombination",
    abstract = "The 12/23 rule requires that V(D)J recombination only occurs between recombination signals with 12 and 23 base pair spacers. We show that the 12/23 rule is established prior to DNA cleavage, by the formation of a synaptic complex containing both 12-spacer and 23-spacer signals. The RAG1 and RAG2 proteins, as well as the DNA bending protein HMG1, are needed for efficient formation of this complex. We show further that the synaptic complex is the functional complex for coupled cleavage. After cleavage, all four broken DNA ends remain associated with the RAG proteins in a postcleavage synaptic complex, whose existence helps to explain the known role of RAG1 and RAG2 in the subsequent end-joining events that complete V(D)J recombination.",
    keywords = "Base composition, DNA, DNA-binding proteins, Gene rearrangement, Genes, Immunoglobulin, High mobility group proteins, Homeodomain proteins, Immunoglobulin J-chains, Immunoglobulin variable Region, Mutation, Protein binding, Recombination, Genetic",
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    language = "English",
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    Assembly of a 12/23 paired signal complex : a critical control point in V(D)J recombination. / Hiom, Kevin; Gellert, Martin (Lead / Corresponding author).

    In: Molecular Cell, Vol. 1, No. 7, 06.1998, p. 1011-1019.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Assembly of a 12/23 paired signal complex

    T2 - a critical control point in V(D)J recombination

    AU - Hiom, Kevin

    AU - Gellert, Martin

    PY - 1998/6

    Y1 - 1998/6

    N2 - The 12/23 rule requires that V(D)J recombination only occurs between recombination signals with 12 and 23 base pair spacers. We show that the 12/23 rule is established prior to DNA cleavage, by the formation of a synaptic complex containing both 12-spacer and 23-spacer signals. The RAG1 and RAG2 proteins, as well as the DNA bending protein HMG1, are needed for efficient formation of this complex. We show further that the synaptic complex is the functional complex for coupled cleavage. After cleavage, all four broken DNA ends remain associated with the RAG proteins in a postcleavage synaptic complex, whose existence helps to explain the known role of RAG1 and RAG2 in the subsequent end-joining events that complete V(D)J recombination.

    AB - The 12/23 rule requires that V(D)J recombination only occurs between recombination signals with 12 and 23 base pair spacers. We show that the 12/23 rule is established prior to DNA cleavage, by the formation of a synaptic complex containing both 12-spacer and 23-spacer signals. The RAG1 and RAG2 proteins, as well as the DNA bending protein HMG1, are needed for efficient formation of this complex. We show further that the synaptic complex is the functional complex for coupled cleavage. After cleavage, all four broken DNA ends remain associated with the RAG proteins in a postcleavage synaptic complex, whose existence helps to explain the known role of RAG1 and RAG2 in the subsequent end-joining events that complete V(D)J recombination.

    KW - Base composition

    KW - DNA

    KW - DNA-binding proteins

    KW - Gene rearrangement

    KW - Genes, Immunoglobulin

    KW - High mobility group proteins

    KW - Homeodomain proteins

    KW - Immunoglobulin J-chains

    KW - Immunoglobulin variable Region

    KW - Mutation

    KW - Protein binding

    KW - Recombination, Genetic

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    DO - 10.1016/S1097-2765(00)80101-X

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    JF - Molecular Cell

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    ER -