Sandbox GGC9: Difference between revisions

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James Nolan, Student

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 == '''Function''' ==
-RAG1 and RAG2 together form the RAG Complex (RAG Recombinases), which are responsible for regulating the DNA cleavage phase during V(D)J recombination. V(D)J recombination functions to produce a plethora of immune molecules in developing B and T immune cells. The B and T cells contain proteins on their surfaces which allow for the recognition of different pathogens and may illicit immune responses. The genes which are responsible for making these proteins have different segments which are V, variable, D, diversity and J, joining. These segments can be combined and rearranged to create the diversity required for the proteins for the B and T cells.  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 to create a double-stranded break between the (RSS) and the adjacent coding sequence. This rearrangement is carried out in the following way: introduction of a nick in the DNA backbone through hairpin formation and then creating a hydroxyl group at the 3' end which attacks the phosphodiester bond on the opposite strand.[1] This mechanism is a direct transesterification reaction which results in four differentiated DNA ends. Histones also assist in the nicking and hairpinning of the strands. The result is the recombination of variable genes joining to produce proteins in a response to different pathogens.[1] Additionally to the role played in V(D)J, RAG also assists B cell allelic exclusion. This means that it is able to silence one allele of the B cell but can silence the other allele. RAG1 also possess ubiquitin properties. Newer Studies suggest that the RAG1/2 recombinase complex acts as a transposon, with similar mechanisms.[2]
+RAG1 and RAG2 together form the RAG Complex (RAG Recombinases), which is responsible for regulating the DNA cleavage phase during V(D)J recombination. V(D)J recombination functions to produce a plethora of immune molecules in developing B and T cells. The B and T immune cells contain proteins on their surfaces which allow for the recognition of different pathogens and elicits proper immune responses. The RAG genes, which are responsible for making these proteins, have different segments which are known as V, variable, D, diversity and J, joining. These segments can be combined and rearranged to create the diversity required for the proteins for the B and T cells.  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. RAG1 is able to  to create a double-stranded break between the (RSS) and the adjacent coding sequence. This rearrangement is carried out in the following way: introduction of a nick in the DNA backbone through hairpin formation and then creating a hydroxyl group at the 3' end which attacks the phosphodiester bond on the opposite strand.[1] This mechanism is a direct transesterification reaction which results in four differentiated DNA ends. Studies of this recombination suggest that the RAG1/2 recombinase complex acts as a transposon, with similar mechanisms.[2] Histones also assist in the nicking and hairpinning of the strands. The result is the recombination of variable genes joining to produce proteins in a response to different pathogens.[1] Additionally to the role played in V(D)J recombination, RAG also assists B cell allelic exclusion which means that it is able to silence one allele of the B cell but can express the other allele. RAG1 also possess ubiquitin properties.
 == '''Disease''' ==
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 Early intervention of people with Omenn's syndrome is important, because if left untreated it will be fatal. [4] Treatment of Omenn's syndrome includes bone marrow or cord blood stem cell transplantation. [4]
 == '''Structural highlights''' ==
 The subunit structure is defined as a homodimer.
-The zinc site plays an important role in DNA cleavage; without the zinc site the DNA would not be able to be cleaved and would not form the essential hairpin structure.[5]
+The zinc site plays an important role in DNA cleavage; without the zinc site the DNA would not be able to be cleaved and would not form the essential hairpin structure.[5]<scene name='75/752271/Zinc_ligands/1'>Zinc Ligands</scene>
-<scene name='75/752271/Zinc_ligands/1'>Zinc Ligands</scene>
+<scene name='75/752271/Zinc_finger_motif/1'>Ring Zinc Finger</scene> of dimerization domain.
+Initial studies identified aspartic acid residues at positions 600 and 708 function to initiate catalysis.[7]<scene name='75/752271/Catalytic_residues/1'>Catalytic Residues</scene>
+In addition to the catalytic function of aspartic acid residues at 600 and 708.
+Researchers have discovered a trio of residues that are necessary for the DNA cleavage during V(D)J recombination. This trio includes the two catalytic residues as well as a Glutamic acid residue at position 962.[8]<scene name='75/752271/Dde_motif/1'>Residues responsible for DNA cleavage</scene>
+Residues 265-383 on RAG 1 contain ubiquitin ligase activity. <scene name='75/752271/Ubiquitin_ligase_activity/1'>Ubiquitin activity</scene>
-Initial studies identified aspartic acid residues at positions 600 and 708 function to initiate catalysis.[7]
-<scene name='75/752271/Catalytic_residues/1'>Catalytic Residues</scene>
-In addition to the catalytic function of aspartic acid residues at 600 and 708, researchers have discovered a trio of residues that are necessary for the DNA cleavage during V(D)J recombination. This trio includes the two catalytic residues as well as a Glutamic acid residue at position 962.[8]
-<scene name='75/752271/Dde_motif/1'>Residues responsible for DNA cleavage</scene>
 </StructureSection>