Abstract

This application is for a new grant to study the mechanism of somatic hypermutation of immunoglobulin (Ig) genes. Our previous work has shown that this process depends on initiation of transcription. The new aims are directed at determining how transcription relates to the somatic mutation process, what the role is of the primary sequence which is the target for mutation and what the cis-acting regulatory elements consist of. Finally, we plan to clone and identify the gene(s) that encode a postulated mutator factor. These studies are important to understand the creation of the lg repertoire with the potential of reacting against any foreign antigen, including tumor antigens. Also, somatic hypermutation has been implicated in autoimmunities. Finally, certain malignant lymphoid tumors arise during the lg gene somatic mutation process and understanding its mechanism will shed light on the tumorigenesis and, hopefully, its prevention.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI047380-03
Application #
6511276
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Kirkham, Perry M
Project Start
2000-05-01
Project End
2005-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
3
Fiscal Year
2002
Total Cost
$416,181
Indirect Cost

  Institution

Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Ratnam, Sarayu; Engler, Peter; Bozek, Grazyna et al. (2014) Identification of Ssm1b, a novel modifier of DNA methylation, and its expression during mouse embryogenesis. Development 141:2024-34
Storb, Ursula (2014) Why does somatic hypermutation by AID require transcription of its target genes? Adv Immunol 122:253-77
Kodgire, Prashant; Mukkawar, Priyanka; Ratnam, Sarayu et al. (2013) Changes in RNA polymerase II progression influence somatic hypermutation of Ig-related genes by AID. J Exp Med 210:1481-92
Kodgire, Prashant; Mukkawar, Priyanka; North, Justin A et al. (2012) Nucleosome stability dramatically impacts the targeting of somatic hypermutation. Mol Cell Biol 32:2030-40
Ratnam, Sarayu; Bozek, Grazyna; Nicolae, Dan et al. (2010) The pattern of somatic hypermutation of Ig genes is altered when p53 is inactivated. Mol Immunol 47:2611-8
Tanaka, Atsushi; Shen, Hong Ming; Ratnam, Sarayu et al. (2010) Attracting AID to targets of somatic hypermutation. J Exp Med 207:405-15
Storb, Ursula; Shen, Hong Ming; Nicolae, Dan (2009) Somatic hypermutation: processivity of the cytosine deaminase AID and error-free repair of the resulting uracils. Cell Cycle 8:3097-101
Shen, Hong Ming; Poirier, Michael G; Allen, Michael J et al. (2009) The activation-induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes but only during transcription. J Exp Med 206:1057-71
Shen, Hong Ming; Bozek, Grazyna; Pinkert, Carl A et al. (2008) Expression of AID transgene is regulated in activated B cells but not in resting B cells and kidney. Mol Immunol 45:1883-92
Longerich, Simonne; Orelli, Brian J; Martin, Richard W et al. (2008) Brca1 in immunoglobulin gene conversion and somatic hypermutation. DNA Repair (Amst) 7:253-66

Showing the most recent 10 out of 25 publications