Martin Gellert, Ph.D.
NIH Distinguished Investigator
Molecular Genetics Section, Laboratory of Molecular Biology
Building 5, Room 241
5 Memorial Drive
Bethesda, MD 20814
We work on the rearrangement of immunoglobulin and T-cell receptor genes, which is essential for the development of lymphoid cells, and for the ability of the immune system to fend off multiple types of attack. This DNA reshuffling, known as V(D)J recombination, makes it possible for us to produce antibodies and T-cell receptors with millions of different specificities. The process is unique in sharing many properties with mobile genetic elements called transposons. It also has similarities with the repair of radiation damage to DNA. Our aim is to understand V(D)J recombination as thoroughly as possible, and then apply this knowledge to the immune system. We now focus on the RAG1 and RAG2 proteins, which work together to break the DNA at specific sites to start recombination. Most recently, we are using structural methods (in collaboration with Dr. Wei Yang of this laboratory) to understand the activities of the RAG proteins. We recently published the first detailed structure of the RAG1-RAG2 complex. We are also learning about covalent modifications of RAG1 by auto-ubiquitylation and by phosphorylation, which alter its activity.
- Ph.D., Columbia University, 1956
- B.A., Harvard University, 1950
Grundy GJ, Yang W, Gellert M. 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. 2010;107(52):22487-92.
Grundy GJ, Ramón-Maiques S, Dimitriadis EK, Kotova S, Biertümpfel C, Heymann JB, Steven AC, Gellert M, Yang W. Initial stages of V(D)J recombination: the organization of RAG1/2 and RSS DNA in the postcleavage complex. Mol Cell. 2009;35(2):217-27.
Kim MS, Lapkouski M, Yang W, Gellert M. Crystal structure of the V(D)J recombinase RAG1-RAG2. Nature. 2015;518(7540):507-11.
Singh SK, Gellert M. Role of RAG1 autoubiquitination in V(D)J recombination. Proc Natl Acad Sci U S A. 2015;112(28):8579-83.
Lapkouski M, Chuenchor W, Kim MS, Gellert M, Yang W. Assembly Pathway and Characterization of the RAG1/2-DNA Paired and Signal-end Complexes. J Biol Chem. 2015;290(23):14618-25.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on May 19th, 2016