RAG1
RAG1 (recombination activating 1) is the catalytic component of the RAG complex, which mediates the DNA cleavage phase of V(D)J recombination in developing B and T lymphocytes. It is also known as RNF74 and was previously named recombination activating gene 1. Browse Assay Genie's current range of RAG1 research reagents below, or read on for the biology behind the target.
V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes by rearranging variable (V), in some cases diversity (D), and joining (J) gene segments. Within the RAG complex, RAG1 mediates DNA binding to the conserved recombination signal sequences (RSS) and catalyses cleavage by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not itself catalytic but is required for all known catalytic activities, so stable binding and cleavage depend on both subunits.
Cleavage proceeds in two steps. A first nick is made in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that attacks the phosphodiester bond on the opposite strand in a direct transesterification reaction. This produces four DNA ends: two hairpin coding ends and two blunt, 5'-phosphorylated ends. Chromatin context matters: histone H3 trimethylated at Lys-4 (H3K4me3) stimulates both the nicking and hairpinning steps.
The RAG complex also contributes to pre-B cell allelic exclusion, which limits expression to a single immunoglobulin heavy chain allele. DNA breaks introduced on one allele induce ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing its recombination. Beyond its endonuclease activity, RAG1 acts as an E3 ubiquitin-protein ligase that monoubiquitinates histone H3, which is required for the joining step of V(D)J recombination, and it mediates polyubiquitination of KPNA1. The RAG1 gene belongs to the RAG1 family and is grouped by HGNC with RING finger E3 ubiquitin protein ligases and RAG transposon-derived genes. Defects in this gene can cause several diseases.
RAG1 drives rearrangement of immunoglobulin and T-cell receptor genes, making it central to studies of B and T lymphocyte development.
RAG1 recognises recombination signal sequences and introduces double-strand breaks via nicking and hairpin formation, a model for studying DNA cleavage chemistry.
The RAG complex contributes to pre-B cell allelic exclusion, enforcing monospecific B-cell receptor expression through ATM-dependent allele repositioning.
RAG1 is an E3 ligase that monoubiquitinates histone H3, linking chromatin modification to the joining step of recombination.
RAG1 is the catalytic component of the RAG complex. It binds recombination signal sequences and introduces a double-strand break between the RSS and the coding segment during V(D)J recombination. RAG2 is required for all known catalytic activities. RAG1 also works as an E3 ubiquitin ligase towards histone H3.
The HGNC name is recombination activating 1, previously recombination activating gene 1. UniProt lists the protein as V(D)J recombination-activating protein 1. Aliases and previous symbols include RNF74 and MGC43321, the former reflecting its RING finger E3 ligase activity.
A mouse ortholog, Rag1, is recorded in the data. NCBI Gene states that defects in the RAG1 gene can be the cause of several diseases. For species reactivity, check the datasheet of any product for its validated reactivity.
RAG2, the essential partner in the RAG complex, and other related targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P15918; product specifications from Assay Genie datasheets.