Department of Biochemistry Box 357350 University of Washington Seattle, WA 98195
 



 
 
 


    
Nancy Maizels
      Professor of Biochemistry
     Professor of Immunology

     206.221.6876 V
     206. 221.6781 F
     maizels@u.washington.edu




 



Research

We study DNA recombination and repair in mammalian cells in two different contexts: in activated B lymphocytes, where genomic structure changes very rapidly during the course of a normal immune response; and in other cells responding to the challenge presented by DNA damage.

In B cells activated by antigen, class switch recombination literally switches one expressed immunoglobulin constant region for another, and somatic hypermutation alters the sequences of immunoglobulin variable regions. We study how switch recombination and somatic hypermutation occur, using approaches that range from hard-core biochemistry to fluorescence microscopy to knockout mice. Recombination/repair proteins that are important in both switch recombination and somatic hypermutation have proven to be essential to maintaining genomic structure in response to DNA damage. This has led us to become interested in the more general roles of some of these proteins, and particularly how they function in maintenance of the G-rich rDNArepeats and G-rich telomeric sequences. Among the proteins we are currently studying are Rad51, Rad52, nucleolin, hnRNP D, and helicases of the RecQ family such as human BLM and yeast Sgs1p.




 

Selected Publications

Duquette ML, Pham P, Goodman MF, Maizels N (2005) AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation. Oncogene 24: 5791-5798.

Larson ED, Cummings WJ, Bednarski DW, Maizels N (2005) MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification. Mol Cell 20: 367-375.

Larson ED, Duquette ML, Cummings WJ, Streiff RJ, Maizels N (2005) MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions. Curr Biol 15: 470-474.

Maizels N (2005) Immunoglobulin gene diversification. Annu Rev Genet 39: 23-46. Yabuki M, Fujii MM, Maizels N (2005) The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions. Nat Immunol 6: 730-736.

Duquette ML, Handa P, Vincent JA, Taylor AF, Maizels N (2004) Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev 18: 1618-1629.

Larson ED, Maizels N (2004) Transcription-coupled mutagenesis by the DNA deaminase AID. Genome Biol 5: 211.

Cocco MJ, Hanakahi LA, Huber MD, Maizels N (2003) Specific interactions of distamycin with G-quadruplex DNA. Nucleic Acids Res 31: 2944-2951.

Maizels N (2003) Yin outwits Yang at the IgE locus. Nat Immunol 4: 7-8.

Huber MD, Lee DC, Maizels N (2002) G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific inhibition. Nucleic Acids Res 30: 3954-3961.

Kong Q, Maizels N (2001) Breaksite batch mapping, a rapid method for assay and identification of DNA breaksites in mammalian cells. Nucleic Acids Res 29: E33.

Kong Q, Maizels N (2001) DNA breaks in hypermutating immunoglobulin genes: evidence for a break-and-repair pathway of somatic hypermutation. Genetics 158: 369-378.

Sun H, Yabuki A, Maizels N (2001) A human nuclease specific for G4 DNA. Proc Natl Acad Sci U S A 98: 12444-12449.

Wu X, Maizels N (2001) Substrate-specific inhibition of RecQ helicase. Nucleic Acids Res 29: 1765-1771.