| First Author | Leduc C | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 10 | Pages | 2925-31 |
| PubMed ID | 20812239 | Mgi Jnum | J:165708 |
| Mgi Id | MGI:4838338 | Doi | 10.1002/eji.201040605 |
| Citation | Leduc C, et al. (2010) Combined deficiency of MSH2 and Smu region abolishes class switch recombination. Eur J Immunol 40(10):2925-31 |
| abstractText | Class switch recombination (CSR) is mediated by G-rich tandem repeated sequences termed switch regions. Transcription of switch regions generates single-stranded R loops that provide substrates for activation-induced cytidine deaminase. Mice deficient in MSH2 have a mild defect in CSR and analysis of their switch junctions has led to a model in which MSH2 is more critical for switch recombination events outside than within the tandem repeats. It is also known that deletion of the whole Smu region severely impairs but does not abrogate CSR despite the lack of detectable R loops. Here, we demonstrate that deficiency of both MSH2 and the Smu region completely abolishes CSR and that the abrogation occurs at the genomic level. This finding further supports the crucial role of MSH2 outside the tandem repeats. It also indicates that during CSR, MSH2 has access to activation-induced cytidine deaminase targets in R-loop-deficient Imu-Cmu sequences rarely used in CSR, suggesting an MSH2-dependent DNA processing activity at the Imu exon that may decrease with transcription elongation across the Smu region. |
