The National Institute of Diabetes & Digestive & Kidney Diseases

We work on the rearrangement of immunoglobulin and T-cell receptor genes (known as V(D)J recombination). This process is essential for the development of lymphoid cells and is unique in sharing some properties with site-specific recombination, and some with the repair of radiation damage to DNA. Our aim is to understand V(D)J recombination as thoroughly as possible, and then to apply this knowledge to the immune system. We showed that recombination begins with site-specific DNA breaks which can be made by the isolated RAG1 and RAG2 proteins, and that a DNA hairpin is produced on one side of each break. This reaction shares many properties with mobile genetic elements (transposons), and we are interested in the potential role of transposition in causing chromosomal translocations of the types found in leukemias and lymphomas. We are also learning about the separate ubiquitin ligase activity of RAG1 and its covalent modification by auto-ubiquitylation.

1. Jones JM Gellert M  Autoubiquitylation of the V(D)J recombinase protein RAG1.  Proc Natl Acad Sci U S A (100): 15446-51, 2003. [Full Text/Abstract]

2. Jones JM Gellert M  Ordered assembly of the V(D)J synaptic complex ensures accurate recombination.  EMBO J (21): 4162-71, 2002. [Full Text/Abstract]

3. Gellert M  V(D)J recombination: RAG proteins, repair factors, and regulation.  Annu Rev Biochem (71): 101-32, 2002. [Full Text/Abstract]

4. Gellert M Hesse JE Hiom K Melek M Modesti M Paull TT Ramsden DA van Gent DC  V(D)J recombination: links to transposition and double-strand break repair.  Cold Spring Harb Symp Quant Biol (64): 161-7, 1999. [Full Text/Abstract]

5. Hiom K Melek M Gellert M  DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations.  Cell (94): 463-70, 1998. [Full Text/Abstract]

6. van Gent DC Ramsden DA Gellert M  The RAG1 and RAG2 proteins establish the 12/23 rule in V(D)J recombination.  Cell (85): 107-13, 1996. [Full Text/Abstract]