Ig gene hypermutation: A mechanism is due

Abstract

Publisher Summary This chapter presents a discussion on Ig gene hypermutation. The chapter reviews (1) the possible participation of some mismatch repair (MMR) components, the mammalian MutS-homologs, (2) the role of Ig gene transcription in the targeting of the process, (3) the occurrence of DNA breaks as specific priming events, (4) the involvement of an error-prone DNA polymerase and the emergence of several new candidate enzymes, and (5) a new partner, activation-induced cytidine deaminase whose molecular contribution is the subject of intense speculation. Several reports have shown that transcription and hypermutation are quantitatively correlated starting with the earlier observation that the hypermutation domain at the heavy chain locus extends over 1 kb downstream from the Ig promoter. From these observations, various models have been proposed in which the transcription complex—as it progresses through the V gene—induces an error-prone repair process. The field of hypermutation is crowded with experiments and models but a precise molecular description of the process is due. The first molecule that seems to be a major player in the process has been discovered after a cDNA subtraction designed to elucidate switch recombination and its putative properties generate many more questions than they bring straightforward explanations.