Martin Frank Gellert, Ph.D.

NIH Distinguished Investigator

Molecular Genetics Section, Laboratory of Molecular Biology

NIDDK

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Building NIHBC 05, Room 241
5 Memorial Dr
Bethesda, MD 20892

+1 301 451 8168

martin.gellert@nih.gov

Research Topics

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.

Biography

  • Ph.D., Columbia University, 1956
  • B.A., Harvard University, 1950

Selected Publications

  1. Chen X, Cui Y, Wang H, Zhou ZH, Gellert M, Yang W. How mouse RAG recombinase avoids DNA transposition. Nat Struct Mol Biol. 2020;27(2):127-133.
  2. Chen X, Cui Y, Best RB, Wang H, Zhou ZH, Yang W, Gellert M. Cutting antiparallel DNA strands in a single active site. Nat Struct Mol Biol. 2020;27(2):119-126.
  3. Kim MS, Chuenchor W, Chen X, Cui Y, Zhang X, Zhou ZH, Gellert M, Yang W. Cracking the DNA Code for V(D)J Recombination. Mol Cell. 2018;70(2):358-370.e4.
  4. 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.
  5. Kim MS, Lapkouski M, Yang W, Gellert M. Crystal structure of the V(D)J recombinase RAG1-RAG2. Nature. 2015;518(7540):507-11.

Related Scientific Focus Areas

This page was last updated on Thursday, November 7, 2024