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. 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 finger motif, which is expendable with respect to the known enzymatic functions as a DNA binding protein and a nuclease. I propose that this domain plays a regulatory role through an activity as an E3 ligase. This is a proposal for the funding of a pilot study to demonstrate that this domain can assist in the ubiquitylation of an artificial substrate in vitro. If this can be achieved, I will test which of the family of E2 proteins best cooperate in the reaction, and pursue the identification of the natural targets in the cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI054356-02
Application #
6719091
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Kirkham, Perry M
Project Start
2003-03-15
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2006-02-28
Support Year
2
Fiscal Year
2004
Total Cost
$83,500
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