ArticleProceedings of the National Academy of Sciences of the United States of America2007
Requirements for DNA hairpin formation by RAG1/2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Cutting antiparallel DNA strands in a single active site.Nature structural & molecular biology · 2020Article
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
- Article
- Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule.Molecular and cellular biology · 2014Article
- DNA bending in the synaptic complex in V(D)J recombination: turning an ancestral transpososome upside down.Discoveries (Craiova, Romania) · 2014Review
- Metabolic sensor AMPK directly phosphorylates RAG1 protein and regulates V(D)J recombination.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- An enzyme-catalyzed multistep DNA refolding mechanism in hairpin telomere formation.PLoS biology · 2013Article
- Integrating prokaryotes and eukaryotes: DNA transposases in light of structure.Critical reviews in biochemistry and molecular biology · 2010Review
- Base flipping in V(D)J recombination: insights into the mechanism of hairpin formation, the 12/23 rule, and the coordination of double-strand breaks.Molecular and cellular biology · 2009Article
- Article
- Article
- Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis.Nature structural & molecular biology · 2009Article
- A non-sequence-specific DNA binding mode of RAG1 is inhibited by RAG2.Journal of molecular biology · 2009Article
- An activation-induced cytidine deaminase-independent mechanism of secondary VH gene rearrangement in preimmune human B cells.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Quantitative analyses of RAG-RSS interactions and conformations revealed by atomic force microscopy.Biochemistry · 2008Article
- Understanding how the V(D)J recombinase catalyzes transesterification: distinctions between DNA cleavage and transposition.Nucleic acids research · 2008Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The rearrangement of antigen receptor genes is initiated by double-strand breaks catalyzed by the RAG1/2 complex at the junctions of recombination signal sequences and coding segments. As with some "cut-and-paste" transposases, such as Tn5 and Hermes, a DNA hairpin is formed at one end of the break via a nicked intermediate. By using abasic DNA substrates, we show that different base positions are important for the two steps of cleavage. Removal of one base in the coding flank enhances hairpin formation, bypassing a requirement for a paired complex of two signal sequences. Rescue by abasic substrates is consistent with a base-flip mechanism seen in the crystal structure of the Tn5 postcleavage complex and may mimic the DNA changes on paired complex formation. We have searched for a tryptophan residue in RAG1 that would be the functional equivalent of W298 in Tn5, which stabilizes the DNA interaction by stacking the flipped base on the indole ring. A W956A mutation in RAG1 had an inhibitory effect on both nicking and hairpin stages that could be rescued by abasic substrates. W956 is therefore a likely candidate for interacting with this base during hairpin formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.