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the ability of the RAG nuclease (show DCLRE1C Proteins) to minimize the risks of genome disruption by coupling the breakage and repair steps of the V(D)J reaction. This implies that the RAG genes, derived from an ancient transposon, have undergone strong selective pressure to prohibit transposition in favor of promoting controlled DNA end joining in cis (show CISH Proteins) by the ubiquitous DNA damage response and DNA repair machineries
We report two siblings with SCID (show PRKDC Proteins) and an atypical phenotype of osteopetrosis (OP (show CSF1 Proteins)). A biallelic microdeletion encompassing the 5' region of TRAF6 (show TRAF6 Proteins), RAG1 (show RAG1 Proteins) and RAG2 genes was identified. TRAF6 (show TRAF6 Proteins), a tumor necrosis factor (show TNF Proteins) receptor-associated family member, plays an important role in T cell signaling and in RANKL (show TNFSF11 Proteins)-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported
The show that DNA damage caused by RAG2 activity in pre-B cells was able to downmodulate RAG2 expression and activity, confirming the existence of a negative feedback regulatory mechanism.
This study reports on the prevalence of RAG1 (show RAG1 Proteins) and RAG2 mutations in ten severe combined immunodeficiency (show PRKDC Proteins) disorder patients in Egypt.
analysis of regions of RAG1 (show RAG1 Proteins) necessary for interaction with RAG2 and measurement of the RAG1 (show RAG1 Proteins)-RAG2 binding affinity
DNA damage triggers relocalization of RAG2 from the nucleus to centrosomes, suggesting a novel mechanism for modulating cellular responses to double strand breaks in developing lymphocytes.
found that Ikaros (show IKZF1 Proteins), a lymphocyte-specific transcription factor, acts as a repressor of NWC promoter--thus identifying a new Ikaros (show IKZF1 Proteins) target--but is insufficient for inducing methylation which depends on the antisense transcription driven by RAG-2 promoter
Investigate the factors that regulate RAG1 (show RAG1 Proteins) and RAG2 cleavage on non-B DNA structures. We find that RAG binding and cleavage on heteroduplex DNA is dependent on the length of the double-stranded flanking region.
The results indicate that the contribution of immune dysregulatory disease due to RAG2 mutations present in the general population may be much higher than previously estimated.
Bidirectional activity of the NWC promoter is responsible for RAG-2 transcription in non-lymphoid cells
This work provides important mechanistic insight into how spatiotemporal expression of the Rag genes is tightly controlled during B lymphocyte (show AKAP17A Proteins) development to prevent mistimed dsDNA breaks and their deleterious consequences.
a novel RAG1 (show RAG1 Proteins)/2-mediated insertion pathway distinct from DNA transposition and trans-V(D)J recombination that destabilizes the genome and shares features with reported oncogenic DNA insertions.
loss of the BH3-only (show BBC3 Proteins) protein BIM (show BCL2L11 Proteins) accelerated lymphoma development in p53 (show TP53 Proteins)-deficient mice. This process was negated by concomitant loss of RAG1 (show RAG1 Proteins)/2-mediated antigen receptor gene rearrangement.
the zinc finger motif within the noncore region of RAG2 is indispensable for maintaining the stability of the RAG2 protein.
evolution of RAG1 (show RAG1 Proteins)/RAG2 began with a Transib transposon whose intrinsic recombination activity was enhanced by capture of an ancestral RAG2, allowing for the development of adaptive immunity.
Rag2(R229Q) knock-in mice developed an inflammatory bowel disease affecting both the small bowel and colon.
Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity.
These results reveal an unanticipated functional interplay between the RAG complex and XLF (show NHEJ1 Proteins) in repairing RAG-induced DNA breaks and maintaining genome integrity during antigen receptor gene assembly.
Based on our results, we propose that interaction of RAG2 with RAG1 (show RAG1 Proteins) induces cooperative interactions of multiple binding sites, induced through conformational changes at the RAG1 (show RAG1 Proteins) interdomain boundary
12recombination signal sequences-23recombination signal sequences cooperation (the "12/23 rule") is important not only for regulating RAG-mediated DNA cleavage but also for the efficiency of RAG1 (show RAG1 Proteins) and RAG2 recruitment to chromatin.
Produced RAG2-knockouts via somatic cell nuclear transfer and analyzed their phenotype. The V(D)J recombination processes were confirmed as being inactivated. They consistently lacked mature T and B cells but had substantial numbers of cells considered to be T- or B-cell progenitors as well as NK cells. They also lacked thymic medulla and lymphoid aggregations in the spleen, mesenteric lymph nodes, and Peyer's patches.
Homozygous RAG1 (show RAG1 Proteins)/2 knockout pigs lack mature B and T lymphocytes; recombination does not occur in the Ig heavy chain (IgH) locus of RAG1 (show RAG1 Proteins)- and RAG2-deficient pigs.
created rag2(E450fs) mutant zebrafish that have reduced numbers of functional T and B cells but are viable and fecund
This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms.
recombination activating gene 2
, recombination activating protein 2
, V(D)J recombination-activating protein 2-like
, V(D)J recombination-activating protein 2
, recombinase activating gene 2
, v(D)J recombination-activating protein 2