In contrast to lower eukaryotes, most vertebrate cells are characterized by a moderate efficiency of homologous recombination (HR) and limited feasibility of targeted genetic modifications. As a notable exception, the chicken DT40 B cell line is distinguished by efficient homology-mediated repair of DNA lesions during Ig gene conversion, and also shows exceptionally high gene-targeting efficiencies. The molecular basis of these phenomena is elusive.
View Article and Find Full Text PDFThe germinal center (GC) reaction has a pivotal function in human B-cell lymphomagenesis. Genetic aberrations occurring during somatic hypermutation and class switch recombination deregulate key factors controlling B-cell physiology and proliferation. Several human lymphoma entities are characterized by a constitutive GC phenotype and ongoing somatic hypermutation, but the molecular basis for this phenomenon is only partly understood.
View Article and Find Full Text PDFDuring secondary immunoglobulin (Ig) diversification in vertebrates, the sequence of the variable region of Ig genes may be altered by templated or non-templated mechanisms. In both cases, cytidine deamination by activation-induced cytidine deaminase (AID) in the transcribed Ig loci leads to DNA lesions, which are repaired by conservative homologous recombination (HR) during Ig gene conversion, or by non-templated mutagenesis during somatic hypermutation. The molecular basis for the differential use of these two pathways in different species is unclear.
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