The adaptive immune system of vertebrates depends upon a DNA recombination system, called V(D)J recombination, to generate the repertoire of immunoglobulin and T- cell receptors. This essential step also leads to chromosomal translocation when misapplied. Much of the regulation of this recombination process occurs at the initial stage when the DNA is cut. The proteins RAG1 and RAG2 form the site-specific nuclease that cuts the appropriate DNA targets and, it is believed, coordinate the recombination reaction. The RAG1 protein possesses a large N-terminal domain, containing a RING motif, which is expendable with respect to the known enzymatic functions as a DNA binding protein and a nuclease. I have shown that this domain can act as an ubiquitin ligase and propose that it plays a regulatory role. This proposal will allow the laboratory to study the interaction between the RAG1 N-terminal domain and several proteins that have been identified through a two-hybrid screen. Several properties will be examined including modification status, induced changes in subcellular localization, protein turn-over and whether the interaction with these proteins influences the choice of recombination targets. Our goal is to identify and characterize protein interactions involving the RAG1 N- terminal domain. These are expected to regulate a critical step in the development of the immune system, and may contribute to genomic instability associated with that process. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI072055-01A1
Application #
7384328
Study Section
Special Emphasis Panel (ZRG1-IMM-B (02))
Program Officer
Rice, Jeffrey S
Project Start
2008-06-01
Project End
2010-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
1
Fiscal Year
2008
Total Cost
$207,500
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461