Sandbox GGC9

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Function

RAG1 and RAG2 form the RAG Complex, 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 creates a double-stranded break between the recombination signal sequences (RSS) and the adjacent coding sequence. This process is executed in the following way: introduction of a nick, creating a 3'-hydroxyl group that 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.

Disease

Relevance

Structural highlights

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