| First Author | Ronai D | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 1 | Pages | 181-90 |
| PubMed ID | 17227912 | Mgi Jnum | J:125291 |
| Mgi Id | MGI:3758133 | Doi | 10.1084/jem.20062032 |
| Citation | Ronai D, et al. (2007) Detection of chromatin-associated single-stranded DNA in regions targeted for somatic hypermutation. J Exp Med 204(1):181-90 |
| abstractText | After encounter with antigen, the antibody repertoire is shaped by somatic hypermutation (SHM), which leads to an increase in the affinity of antibodies for the antigen, and class-switch recombination (CSR), which results in a change in the effector function of antibodies. Both SHM and CSR are initiated by activation-induced cytidine deaminase (AID), which deaminates deoxycytidine to deoxyuridine in single-stranded DNA (ssDNA). The precise mechanism responsible for the formation of ssDNA in V regions undergoing SHM has yet to be experimentally established. In this study, we searched for ssDNA in mutating V regions in which DNA-protein complexes were preserved in the context of chromatin in human B cell lines and in primary mouse B cells. We found that V regions that undergo SHM were enriched in short patches of ssDNA, rather than R loops, on both the coding and noncoding strands. Detection of these patches depended on the presence of DNA-associated proteins and required active transcription. Consistent with this, we found that both DNA strands in the V region were transcribed. We conclude that regions of DNA that are targets of SHM assemble protein-DNA complexes in which ssDNA is exposed, making it accessible to AID. |
