Gene Recombination

Immunoglobin genes are composed of separated segments of DNA that become join together in the process called somatic recombination to make a functional gene.In heavy chain genes there are 3 gene segments the Variable or V segment, the diversity or D segment and joining the J segment.Light chain genes have only 2 gene segments V and J segments

Gene segments that can be recombined has specific sequence motifs adjacent to them called Recombination Signal sequence or RSS motifs .The protein complex containing the products of the recombination activated genes RAG1 and RAG2 binds specifically to the RSS motif.
The individual gene segments to whose flanking RSS motif the RAG protein complex binds are selected at random from the number of copies present in each gene locus .The RAG protein complex brings together the gene segments to be recombined and cleave the DNA exactly at the junction of gene segments and adjoining RSS motifs .The cleavage creates a Hair pin of DNA at the end of the gene segments and double stranded breaks at the end of RSS motifs.

Additional proteins DNA -dependent protein kinase(DNA-PK),Ku,Artemis and dimer of DNA ligase/XRCC4 dimer are incorporated into larger complex with RAG proteins. These RSS ends are joined forming signal joints to create closed circular DNA that plays no further role in the recombination process.

DNA hairpins at the end of the gene segments are cleaved, an additional enzyme Terminal deoxynucleotidyltransferase (TdT) is recruited and adds additional nucleotide to ends of nucleotide strands, The other enzymes in the complex ligate together the two ends of the DNA segment completing the recombination process.