W. Jason Cummings

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Immunoglobulin class switch recombination joins a new constant (C) region to the rearranged and expressed heavy chain variable (VDJ) region in antigen-activated B cells (Figure 1A) (reviewed in [1, 2]). Switch recombination is activated by transcription of intronic, G-rich and repetitive switch (S) regions and produces junctions that are heterogeneous in(More)
MRE11/RAD50/NBS1 (MRN) is a ubiquitous complex that participates in the response to DNA damage and in immunoglobulin (Ig) gene diversification. Ig gene diversification is initiated by deamination of cytosine to uracil, followed by removal of uracil to create an abasic (AP) site. We find that MRE11 associates specifically with rearranged Ig genes in(More)
Homology-directed repair is a powerful mechanism for maintaining and altering genomic structure. We asked how chromatin structure contributes to the use of homologous sequences as donors for repair using the chicken B cell line DT40 as a model. In DT40, immunoglobulin genes undergo regulated sequence diversification by gene conversion templated by(More)
Rearranged Ig genes undergo diversification in sequence and structure initiated by the DNA deaminase, activation-induced deaminase. Ig genes must be transcribed for diversification to occur, but whether there are additional requirements for cis activation has not been established. Here we show, by chromatin immunoprecipitation, that the regulatory factor(More)
Homologous recombination is essential for maintaining genomic integrity. A common repair mechanism, it uses a homologous or homeologous donor as a template for repair of a damaged target gene. Such repair must be regulated, both to identify appropriate donors for repair, and to avoid excess or inappropriate recombination. We show that modifications of donor(More)
The human serine protease inhibitor (serpin) gene cluster at 14q32.1 is a useful model system to study cell-type-specific gene expression and chromatin structure. Activation of the serpin locus can be induced in vitro by transferring human chromosome 14 from non-expressing to expressing cells. Serpin gene activation in expressing cells is correlated with(More)
C. Bochna,1 B. P. Terburg,1 D. J. Abbott,2 A. Ahmidouch,3 C. S. Armstrong,4 J. Arrington,5 K. A. Assamagan,6 O. K. Baker,2,6 S. P. Barrow,7 D. P. Beatty,7 D. H. Beck,1 S. Y. Beedoe,8 E. J. Beise,9 J. E. Belz,10 P. E. Bosted,11 E. J. Brash,12,18 H. Breuer,9 R. V. Cadman,1 L. Cardman,2 R. D. Carlini,2 J. Cha,6 N. S. Chant,9 G. Collins,9 C. Cothran,13 W. J.(More)
Complement activation via the lectin activation pathway (LP) has been identified as the key mechanism behind post-ischemic tissue inflammation causing ischemia-reperfusion injury (IRI) which can significantly impact the clinical outcome of ischemic disease. This work defines the contributions of each of the three LP-associated enzymes—mannan-binding(More)
Gene conversion depends upon the same factors that carry out more general process of homologous recombination, including homologous gene targeting and recombinational repair. Among these are the RAD51 paralogs, conserved factors related to the key recombination factor, RAD51. In chicken and other fowl, gene conversion (templated mutation) diversifies(More)
Monoclonal antibodies (mAbs) can be potent and highly specific therapeutics, diagnostics and research reagents. Nonetheless, mAb discovery using current in vivo or in vitro approaches can be costly and time-consuming, with no guarantee of success. We have established a platform for rapid discovery and optimization of mAbs ex vivo. This DTLacO platform(More)