A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif

Abstract

SITE-SPECIFIC recombination requires conserved DNA sequences specific to each system, and system-specific proteins that recognize specific DNA sequences. The site-specific recombinases seem to fall into at least two families, based on their protein structure and chemistry of strand breakage (reviewed in ref. 1). One of these is the resolvase-invertase family, members of which seem to form a serine-phosphate linkage with DNA. Members of the other family, called the integrase family, contain a conserved tyrosine residue that forms a covalent linkage with the 3'-phosphate of DNA at the site of recombination. Structural comparison of integrases shows that these proteins share a highly conserved 40-residue motif2. V-(D)-J recombination of the immunoglobulin gene requires conserved recombination signal sequences (RS) of a hep-tamer CACTGTG and a T-rich nonamer GGTTTTTGT, which are separated by a spacer sequence of either 12 or 23 bases (reviewed in refs 3 and 4). We have recently purified, almost to homogeneity, a protein that specifically binds to the immunoglobulin Jk RS containing the 23-base-pair spacer sequence5. By synthesizing probes on the basis of partial amino-acid sequences of the purified protein, we have now isolated and characterized the complementary DNA of this protein. The amino-acid sequence deduced from the cDNA sequence reveals that the Jk RS-binding protein has a sequence similar to the 40-residue motif of integrases of phages, bacteria and yeast, indicating that this protein could be involved in V-(D)-Jrecombination as a recombinase.