Our research program aimed at understanding the functions of the RAG1-RAG2 protein complex in molecular detail has progressed in the past year. Our crystal structure of the proteins without DNA (2015) was a major advance, but left questions about mechanism unanswered. Although we were able to give an explanation of the so called 12/23 rule in V(D)J recombination by modeling appropriate DNA fragments into the structure, it was essential to obtain detailed information on structures containing DNA at all stages of the cleavage reaction. Crystals of several of these species have now been obtained and are in the process of being further refined. Our work on RAG mutations that are known to cause severe combined immune deficiency (SCID), or a variant form of the same disorder known as Omenn syndrome is also continuing, with further analysis of specific mutated residues.
| Kim, Min-Sung; Chuenchor, Watchalee; Chen, Xuemin et al. (2018) Cracking the DNA Code for V(D)J Recombination. Mol Cell 70:358-370.e4 |
| Lapkouski, Mikalai; Chuenchor, Watchalee; Kim, Min-Sung et al. (2015) Assembly Pathway and Characterization of the RAG1/2-DNA Paired and Signal-end Complexes. J Biol Chem 290:14618-25 |
| Kim, Min-Sung; Lapkouski, Mikalai; Yang, Wei et al. (2015) Crystal structure of the V(D)J recombinase RAG1-RAG2. Nature 518:507-11 |
| Singh, Samarendra K; Gellert, Martin (2015) Role of RAG1 autoubiquitination in V(D)J recombination. Proc Natl Acad Sci U S A 112:8579-83 |
| Um, Jee-Hyun; Brown, Alexandra L; Singh, Samarendra K et al. (2013) Metabolic sensor AMPK directly phosphorylates RAG1 protein and regulates V(D)J recombination. Proc Natl Acad Sci U S A 110:9873-8 |
| Gupta, Shikha; Gellert, Martin; Yang, Wei (2011) Mechanism of mismatch recognition revealed by human MutS? bound to unpaired DNA loops. Nat Struct Mol Biol 19:72-8 |
| Dayal, Sandeep; Nedbal, Jakub; Hobson, Philip et al. (2011) High resolution analysis of the chromatin landscape of the IgE switch region in human B cells. PLoS One 6:e24571 |
| Grundy, Gabrielle J; Yang, Wei; Gellert, Martin (2010) Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination. Proc Natl Acad Sci U S A 107:22487-92 |
| Grundy, Gabrielle J; Ramón-Maiques, Santiago; Dimitriadis, Emilios K et al. (2009) Initial stages of V(D)J recombination: the organization of RAG1/2 and RSS DNA in the postcleavage complex. Mol Cell 35:217-27 |
| Longo, Nancy S; Grundy, Gabrielle J; Lee, Jisoo et al. (2008) An activation-induced cytidine deaminase-independent mechanism of secondary VH gene rearrangement in preimmune human B cells. J Immunol 181:7825-34 |
