The RAG recombinase: Beyond breaking

RAG Recombinase as a Selective Pressure for Genome Evolution

The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact w...

The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells

The emergence of recombination-activating genes (RAGs) in jawed vertebrates endowed adaptive immune cells with the ability to assemble a diverse set of antigen receptor genes. In contrast, innate lymphocytes, such as natural killer (NK) cells, are not believed to require RAGs. Here, we report that NK cells unable to express RAGs or RAG endonuclease activity during ontogeny exhibit a cell-intrin...

Activated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes

To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras-RAG). Similar to the effects of an immunoglobulin (Ig) mu heavy chain (HC) transgene, activated Ras caused progression of RAG1-deficient progenitor (pro)-...

Independent of the Rag Proteins Beyond the 12/23 Rule of VDJ Recombination

Radiative Electroweak Symmetry Breaking Beyond Leading Logarithms

The top-quark Yukawa coupling is too large to permit radiative electroweak symmetry breaking to occur for small values of y, the Higgs self-coupling, to leading-logarithm order. However, a large y solution leading to a viable Higgs mass of approximately 220GeV does exist, and differs from conventional symmetry breaking by an approximately five-fold enhancement of the Higgs self-coupling. This s...