Chapter 20 - Molecular Mechanism of Class Switch Recombination

Abstract

This chapter describes the latest knowledge about the molecular mechanism of class switch recombination (CSR), focusing on the functional role of activation cytidine deaminase (AID) in CSR. Extensive studies have revealed several critical features of the molecular mechanism of CSR. First, CSR is dependent on the highly repetitive S-region sequences, occurring anywhere within the repeats, thus being a region-specific recombination. Second, CSR takes place only when the S region is actively transcribed. Therefore, isotype specificity is determined by the regulation of transcription through the S region. Third, CSR is initiated by two nicking cleavages, generating a staggered double strand breaks (DSB). Fourth, CSR is completely dependent on the AID activity. Fifth, current evidence indicates that the repair of the cleaved ends utilizes the non-homologous end-joining (NHEJ) repair system. Sixth, other repair proteins such as mismatch repair, base excision repair, and γ-H2AX are required for efficient CSR. It is important to conclusively determine whether AID itself can deaminate deoxyribonucleic acid (DNA) or whether AID edits an mRNA precursor for a cleaving enzyme. This will lead to the identification of the molecular nature of the cleaving enzyme. It is equally critical to identify the components of the putative recombinase complex and to understand how it is targeted to S regions. These conclusions will inevitably lead to the understanding of how the molecular mechanism of CSR differs from that of SHM.