Molecular Analysis of DNA Rearrangements in the Immune System

Abstract

USACover illustration: V(D)J recombination is one of three covalent alterations of DNA that generate the genes encoding antigen receptors of the immune system. Class switch recombination and somatic hypermutation are two others. All three, and related topics, are discussed in this volume.The cover is a partial model for V(D)J recombination. The yellow circles represent the RAG-7,-2 endonuclease. This endonuclease cleaves at heptamer/nonamer signal sequences that have either a 72-or 23-base pair spacer between the heptamer and the nona mer (green and red triangles, respectively). The endonuclease generates a hairpinned coding end and a blunt signal end. Ku70/BO, a heterodimer, is the predominant DNA end binding protein in cells and is thought to bind to DNA termini. In one model, Ku is the DNA binding component of a complex that includes the DNA-dependent protein kinase, DNA-PKcs. DNA-PKcs appears to be the defective component in the doublestrand break repair complementation group XRCC7. XRCC7 also is the complementation group for murine SCID. Ku70 is defective in XRCC6, KuBO is defective in XRCC5. In V(D)J recombination, the signal ends are joined to form a signal joint. The V and J sub-exons are joined to form the coding joint, creating a novel exon in the immune-specific repertoire armamentarium.