Sandbox GGC9: Difference between revisions
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== Function == | == Function == | ||
RAG1 and RAG2 form the RAG Complex (RAG Recombinases), which is responsible for regulating the DNA cleavage phase during recombination. V(D)J recombination functions to produce a plethora of immune molecules in developing B and T-lymphocytes. The V stands for variable, D, diversity and J joining. RAG1 functions as the catalytic portion while RAG2, although not catalytic, is required for RAG1 to function. RAG1 controls the ability of the DNA to bind to the RSS or recombination signal sequences. This is achieved by the ability of the RAG1 complex to create a double-stranded break between the (RSS) and the adjacent coding sequence. This process is executed in the following way: introduction of a nick, creating a 3'-hydroxyl group which attacks the phosphodiester bond on the opposite strand. This is a direct transesterification reaction which results in four DNA ends. Histones also assist in the nicking and hairpinning of the strands. The result is the recombination of variable genes joining. Additionally to the role played in V(D)J, RAG also assists in pre-B cell allelic exclusion. This means that there is a recombination of the second allele. RAG1 also possess ubiquitin properties. | RAG1 and RAG2 form the RAG Complex (RAG Recombinases), which is responsible for regulating the DNA cleavage phase during recombination. V(D)J recombination functions to produce a plethora of immune molecules in developing B and T-lymphocytes. The V stands for variable, D, diversity and J joining of the gene segments. RAG1 functions as the catalytic portion while RAG2, although not catalytic, is required for RAG1 to function.[1] RAG1 controls the ability of the DNA to bind to the RSS or recombination signal sequences. This is achieved by the ability of the RAG1 complex to create a double-stranded break between the (RSS) and the adjacent coding sequence. This process is executed in the following way: introduction of a nick, creating a 3'-hydroxyl group which attacks the phosphodiester bond on the opposite strand.[1] This is a direct transesterification reaction which results in four DNA ends. Histones also assist in the nicking and hairpinning of the strands. The result is the recombination of variable genes joining.[1] Additionally to the role played in V(D)J, RAG also assists in pre-B cell allelic exclusion. This means that there is a recombination of the second allele. RAG1 also possess ubiquitin properties. Newer Studies suggest that the RAG1/2 recombinase complex acts as a domesticated transposase.[2] | ||
== Disease == | == Disease == | ||
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<references/> | <references/> | ||
( | [1] Grazini U, Zanardi F, Citterio E, Casola S, Goding CR, McBlane F. The RING domain of RAG1 ubiquitylates histone H3: a novel activity in chromatin-mediated regulation of V(D)J joining. Mol Cell. 2010 Jan 29;37(2):282-93. doi: 10.1016/j.molcel.2009.12.035. PMID: 20122409. | ||
[2] Zhang Y, Corbett E, Wu S, Schatz DG. Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase. EMBO J. 2020 Nov 2;39(21):e105857. doi: 10.15252/embj.2020105857. Epub 2020 Sep 18. PMID: 32945578; PMCID: PMC7604617. | |||