Nucleic Acids Research, 1995, Vol. 23, No. 6 1060-1067
© 1995
MOLECULAR BIOLOGY |
Coding sequence composition flanking either signal element alters V(D)J recombination efficiency
Division of Tumor Immunology, Dana-Farber Cancer Institute and Department of Microbiology and Molecular Genetics, Harvard Medical School Boston, MA 02115, USA
*To whom correspondence should be addressed
Received August 29, 1994. Revised January 4, 1995. Accepted January 4, 1995.
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.
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