ArticleMolecular and cellular biology2009
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.
Article in Molecular and cellular biology, 2009. 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.
- RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination.Cell reports · 2021Article
- Jumping Ahead withViruses · 2021Review
- A single amino acid switch converts the Sleeping Beauty transposase into an efficient unidirectional excisionase with utility in stem cell reprogramming.Nucleic acids research · 2020Article
- A single active site in the mariner transposase cleaves DNA strands of opposite polarity.Nucleic acids research · 2017Article
- Article
- Biochemical Characterization of Kat1: a Domesticated hAT-Transposase that Induces DNA Hairpin Formation and MAT-Switching.Scientific reports · 2016Article
- Article
- The architecture of the 12RSS in V(D)J recombination signal and synaptic complexes.Nucleic acids research · 2015Article
- V(D)J Recombination: Mechanism, Errors, and Fidelity.Microbiology spectrum · 2014Review
- Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule.Molecular and cellular biology · 2014Article
- Crosstalk between transposase subunits during cleavage of the mariner transposon.Nucleic acids research · 2014Article
- RAG and HMGB1 create a large bend in the 23RSS in the V(D)J recombination synaptic complexes.Nucleic acids research · 2013Article
- H-NS mediates the dissociation of a refractory protein-DNA complex during Tn10/IS10 transposition.Nucleic acids research · 2011Article
- A simple topological filter in a eukaryotic transposon as a mechanism to suppress genome instability.Molecular and cellular biology · 2011Article
- Delivering the goods: viral and non-viral gene therapy systems and the inherent limits on cargo DNA and internal sequences.Genetica · 2010Review
- Transposition of the human Hsmar1 transposon: rate-limiting steps and the importance of the flanking TA dinucleotide in second strand cleavage.Nucleic acids research · 2010Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Tn5 transposase cleaves the transposon end using a hairpin intermediate on the transposon end. This involves a flipped base that is stacked against a tryptophan residue in the protein. However, many other members of the cut-and-paste transposase family, including the RAG1 protein, produce a hairpin on the flanking DNA. We have investigated the reversed polarity of the reaction for RAG recombination. Although the RAG proteins appear to employ a base-flipping mechanism using aromatic residues, the putatively flipped base is not at the expected location and does not appear to stack against any of the said aromatic residues. We propose an alternative model in which a flipped base is accommodated in a nonspecific pocket or cleft within the recombinase. This is consistent with the location of the flipped base at position -1 in the coding flank, which can be occupied by purine or pyrimidine bases that would be difficult to stabilize using a single, highly specific, interaction. Finally, during this work we noticed that the putative base-flipping events on either side of the 12/23 recombination signal sequence paired complex are coupled to the nicking steps and serve to coordinate the double-strand breaks on either side of the complex.
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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.