Stimulation of V(D)J cleavage by high mobility group proteins

Dik C. van Gent, Kevin Hiom, Tanya T. Paull, Martin Gellert (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    204 Citations (Scopus)

    Abstract

    V(D)J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2 proteins initiate the reaction by making double-strand DNA breaks at both signals, and must thus be able to operate on these two different spatial arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding at the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar array of RAG proteins could accommodate a signal with either a 12 or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled cleavage greatly when both signal sequences are present, suggesting that these proteins also aid the formation of a synaptic complex.

    Original languageEnglish
    Pages (from-to)2665-2670
    Number of pages6
    JournalEMBO Journal
    Volume16
    Issue number10
    DOIs
    Publication statusPublished - 15 May 1997

    Fingerprint

    High Mobility Group Proteins
    Protein Sorting Signals
    HMGB2 Protein
    V(D)J Recombination
    HMGB1 Protein
    DNA
    Protein Array Analysis
    Proteins
    Double-Stranded DNA Breaks
    Protein Binding

    Keywords

    • Binding sites
    • DNA
    • DNA-binding proteins
    • Gene rearrangement, T-Lymphocyte
    • High mobility group proteins
    • Homeodomain proteins
    • Models, Genetic
    • Nucleic acid conformation
    • Protein binding
    • Receptors, Antigen, T-Cell
    • Recombination, Genetic

    Cite this

    van Gent, Dik C. ; Hiom, Kevin ; Paull, Tanya T. ; Gellert, Martin. / Stimulation of V(D)J cleavage by high mobility group proteins. In: EMBO Journal. 1997 ; Vol. 16, No. 10. pp. 2665-2670.
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    title = "Stimulation of V(D)J cleavage by high mobility group proteins",
    abstract = "V(D)J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2 proteins initiate the reaction by making double-strand DNA breaks at both signals, and must thus be able to operate on these two different spatial arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding at the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar array of RAG proteins could accommodate a signal with either a 12 or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled cleavage greatly when both signal sequences are present, suggesting that these proteins also aid the formation of a synaptic complex.",
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    Stimulation of V(D)J cleavage by high mobility group proteins. / van Gent, Dik C.; Hiom, Kevin; Paull, Tanya T.; Gellert, Martin (Lead / Corresponding author).

    In: EMBO Journal, Vol. 16, No. 10, 15.05.1997, p. 2665-2670.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Stimulation of V(D)J cleavage by high mobility group proteins

    AU - van Gent, Dik C.

    AU - Hiom, Kevin

    AU - Paull, Tanya T.

    AU - Gellert, Martin

    PY - 1997/5/15

    Y1 - 1997/5/15

    N2 - V(D)J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2 proteins initiate the reaction by making double-strand DNA breaks at both signals, and must thus be able to operate on these two different spatial arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding at the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar array of RAG proteins could accommodate a signal with either a 12 or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled cleavage greatly when both signal sequences are present, suggesting that these proteins also aid the formation of a synaptic complex.

    AB - V(D)J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2 proteins initiate the reaction by making double-strand DNA breaks at both signals, and must thus be able to operate on these two different spatial arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding at the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar array of RAG proteins could accommodate a signal with either a 12 or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled cleavage greatly when both signal sequences are present, suggesting that these proteins also aid the formation of a synaptic complex.

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    KW - DNA

    KW - DNA-binding proteins

    KW - Gene rearrangement, T-Lymphocyte

    KW - High mobility group proteins

    KW - Homeodomain proteins

    KW - Models, Genetic

    KW - Nucleic acid conformation

    KW - Protein binding

    KW - Receptors, Antigen, T-Cell

    KW - Recombination, Genetic

    U2 - 10.1093/emboj/16.10.2665

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    M3 - Article

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