Abstract

The unifying goal of this proposal is to break down the hypermutation process into separate events, which can then be studied in mechanistic detail.
Each aim proposes an independent strategy directed toward this goal.
The aims are: 1. study the role of DNA lesions in hypermutation; 2. determine the function of mismatch repair in hypermutation; 3. develop extrachromosomal substrates for active, targeted hypermutation; and 4. identify and characterize activities essential for the regulation or initiation of hypermutation. The significance of these aims, when achieved, is that they will provide an understanding of this key process. This will also provide molecular targets which can be manipulated to enhance or modulate diseases states, including autoimmune diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM041712-13
Application #
6329708
Study Section
Special Emphasis Panel (ZRG2-GNM (03))
Program Officer
Wolfe, Paul B
Project Start
1989-12-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
13
Fiscal Year
2001
Total Cost
$258,371
Indirect Cost

  Institution

Name
University of Washington
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Le, Quy; Maizels, Nancy (2015) Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID. PLoS Genet 11:e1005411
Maizels, Nancy (2013) Genome engineering with Cre-loxP. J Immunol 191:5-6
Humbert, Olivier; Davis, Luther; Maizels, Nancy (2012) Targeted gene therapies: tools, applications, optimization. Crit Rev Biochem Mol Biol 47:264-81
Yabuki, Munehisa; Cummings, W Jason; Leppard, John B et al. (2012) Antibody discovery ex vivo accelerated by the LacO/LacI regulatory network. PLoS One 7:e36032
Sacho, Elizabeth J; Maizels, Nancy (2011) DNA repair factor MRE11/RAD50 cleaves 3'-phosphotyrosyl bonds and resects DNA to repair damage caused by topoisomerase 1 poisons. J Biol Chem 286:44945-51
Davis, Luther; Maizels, Nancy (2011) DNA nicks promote efficient and safe targeted gene correction. PLoS One 6:e23981
Eddy, Johanna; Vallur, Aarthy C; Varma, Sudir et al. (2011) G4 motifs correlate with promoter-proximal transcriptional pausing in human genes. Nucleic Acids Res 39:4975-83
Yabuki, Munehisa; Ordinario, Ellen C; Cummings, W Jason et al. (2009) E2A acts in cis in G1 phase of cell cycle to promote Ig gene diversification. J Immunol 182:408-15
Ordinario, Ellen C; Yabuki, Munehisa; Larson, Ryan P et al. (2009) Temporal regulation of Ig gene diversification revealed by single-cell imaging. J Immunol 183:4545-53
Ordinario, Ellen C; Yabuki, Munehisa; Handa, Priya et al. (2009) RAD51 paralogs promote homology-directed repair at diversifying immunoglobulin V regions. BMC Mol Biol 10:98

Showing the most recent 10 out of 30 publications