Coding sequence composition flanking either signal element alters V(D)J recombination efficiency

ABSTRACT Lymphoid V(D)J rearrangement is targeted by recombination signal sequences (RSS) bordering V, D or J exons. We demonstrate that the DNA composition of flanking coding positions, particularly poly(A) or poly(T) stretches at one or both RSS, diminishes V(D)J recombination up to 100-fold. Posi...

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Veröffentlicht in:	Nucleic acids research 1995-03, Vol.23 (6), p.1060-1067
Hauptverfasser:	Boubnov, Nikolai V., Wills, Zachary P., Weaver, David T.
Format:	Artikel
Sprache:	eng
Schlagworte:	B-Lymphocytes - enzymology Base Sequence DNA Nucleotidyltransferases - metabolism Gene Rearrangement, B-Lymphocyte - genetics Integrases Molecular Sequence Data Oligodeoxyribonucleotides - genetics Recombinases Recombination, Genetic - genetics Templates, Genetic Tumor Cells, Cultured
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Zusammenfassung:	ABSTRACT Lymphoid V(D)J rearrangement is targeted by recombination signal sequences (RSS) bordering V, D or J exons. We demonstrate that the DNA composition of flanking coding positions, particularly poly(A) or poly(T) stretches at one or both RSS, diminishes V(D)J recombination up to 100-fold. Positionally correct cleavages occur in the inhibited reactions, since the junctions formed show the same frequency of precision as uninhibited reactions. Open/shut cleavage/rejoining is not increased at a normal RSS in substrates containing inhibitory A/T homopolymers versus random sequence at a second RSS. Thus recombinase action at both cleavage sites is severely disrupted by modified coding sequences.
ISSN:	0305-1048 1362-4962
DOI:	10.1093/nar/23.6.1060