what is RAG genes?

Answer 1

Recombination activating gene
The recombination activating genes encode enzymes that play an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the process of VDJ recombination. There are two recombination activating gene products known as RAG-1 and RAG-2, whose cellular expression is restricted to lymphocytes during their developmental stages. RAG-1 and RAG-2 are essential to the generation of mature B and T lymphocytes, two cell types that are crucial components of the adaptive immune system.

Function of RAG proteins
RAG enzymes work as a multi-subunit complex to induce cleavage of a single double stranded DNA (dsDNA) molecule between the antigen receptor coding segment and a flanking recombination signal sequence (RSS). They do this in two steps. They initially introduce a ‘nick’ in the 5' (upstream) end of the RSS heptamer (a conserved region of 7 nucleotides) that is adjacent to the coding sequence, leaving behind a specific biochemical structure on this region of DNA; a 3'-hydroxyl (OH) group at the coding end and a 5'-phosphate (PO4) group at the RSS end. The next step couples these chemical groups, binding the OH-group (on the coding end) to the PO4-group (that is sitting between the RSS and the gene segment on the opposite strand). This produces a 5'-phosphorylated double-stranded break at the RSS and a covalently closed hairpin at the coding end. The RAG proteins remain at these junctions until other enzymes repair the DNA breaks.

The RAG proteins initiate V(D)J recombination, which is essential for the maturation of pre-B and pre-T cells. Activated mature B cells also possess two other remarkable, RAG independent, phenomena of manipulating their own DNA; so-called class-switch recombination (AKA isotype switching) and somatic hypermutation (AKA affinity maturation).

Structure of RAG proteins
As with many enzymes, RAG proteins are fairly large. For example, mouse RAG-1 contains 1040 amino acids and mouse RAG-2 contains 527 amino acids. The enzymatic activity of the RAG proteins is largely concentrated in a core region; residues 384–1008 of RAG-1 and residues 1–387 of RAG-2 retain most of the DNA cleavage activity. The RAG-1 core contains three acidic residues (D600, D708, and E962) in what is called the DDE motif, the major active site for DNA cleavage. These residues are critical for nicking the DNA strand and for forming the DNA hairpin. Residues 384–454 of RAG-1 comprise a nonamer-binding region (NBR) that specifically binds the conserved nonomer (9 nucleotides) of the RSS and the central domain (amino acids 528–760) of RAG-1 binds specifically to the RSS heptamer. The core region of RAG-2 is predicted to form a six-bladed beta-propeller structure that appears less specific than RAG-1 for its target.

Answer 2

Antibodies (for B cell receptor-BCR) and T cell receptors (TCR) are supposed to be specific for one antigen only. However, there are over 1 billion possible antigens yet there are about 30, 000 genes in the humans, and of course, only a small fraction of this is used for antibodies and TCRs. So, the question is how then can the body make so many receptors with so few genes?
The answer lies in genetic recombination of B and T cell immunoglobulin receptors known as V(D)J recombination. Basically, B and T immunoglobulin genes contain several hundred (V) variable segments, several (D) diversity segments (in heavy chains), and several (J) joining segments. Probability shows that different V, D, and J segments can recombine in millions of combinations.
To answer your question, recombination activating genes 1 and 2 (RAG1 and RAG2) code for enzymes with the same name that are responsible for breaking DNA at specific sequences, which allows removal of and combinations of different V,( D), and J segments. V (D) J recombination + other mechanism are responsible for generating the diversity in B and TCRs.
People who have defective RAGs end up with primary immunodeficiencies. These people can't protect themselves from simple bacterial infections and sometimes have to be put in protective environments. On the opposite side, other people may have over-active or uncontrolled RAG genes, which cause aberrant recombination and hence cancers.

Answer 3

"The Human Immune System functions due to the ability of B cells and T cells to recognize Antigens and create the necessary response to neutralize the pathogen. Antigens are recognized in the body through highly specific interactions with the variable immnoglobulin domains on B cells and the T cell receptor region of T cells. Through the process of somatic recombination a variety of specific immunoglobulin domains and T cell receptors can be created with minimal genetic requirements. The Recombination Activating proteins RAG -1 and RAG-2 act together as a heterodimer in the initiation of the process of antigen receptor gene segment assembly. (Spanopoulou, 1996). These proteins are encoded by the Recombination Activating genes, which are found on human chromosome 11 (Shigeoka, 2002). The RAG genes are in very close proximity and consist of one exon (Janeway, 2001). These proteins are essential for proper formation and function of B cell and T cell receptors. (Janeway, 2001)These proteins are active only in the very early stages of lymphoid development as part of the V(D)J recombinase. These enzymes act together to effect somatic recombination. The RAG complex is responsible for initiating the recombination of the variable (V), diversity (D) and joining (J) gene segments of the receptor (Janeway 2001)."

Answer 4

The recombination activating genes encode enzymes that play an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the process of VDJ recombination. There are two recombination activating gene products known as RAG-1 and RAG-2, whose cellular expression is restricted to lymphocytes during their developmental stages. RAG-1 and RAG-2 are essential to the generation of mature B and T lymphocytes, two cell types that are crucial components of the adaptive immune system.

Function of RAG proteins:
RAG enzymes work as a multi-subunit complex to induce cleavage of a single double stranded DNA (dsDNA) molecule between the antigen receptor coding segment and a flanking recombination signal sequence (RSS). They do this in two steps. They initially introduce a ‘nick’ in the 5' (upstream) end of the RSS heptamer (a conserved region of 7 nucleotides) that is adjacent to the coding sequence, leaving behind a specific biochemical structure on this region of DNA; a 3'-hydroxyl (OH) group at the coding end and a 5'-phosphate (PO4) group at the RSS end. The next step couples these chemical groups, binding the OH-group (on the coding end) to the PO4-group (that is sitting between the RSS and the gene segment on the opposite strand). This produces a 5'-phosphorylated double-stranded break at the RSS and a covalently closed hairpin at the coding end. The RAG proteins remain at these junctions until other enzymes repair the DNA breaks.

The RAG proteins initiate V(D)J recombination, which is essential for the maturation of pre-B and pre-T cells. Activated mature B cells also possess two other remarkable, RAG independent, phenomena of manipulating their own DNA; so-called class-switch recombination (AKA isotype switching) and somatic hypermutation (AKA affinity maturation).

Structure of RAG proteins:
As with many enzymes, RAG proteins are fairly large. For example, mouse RAG-1 contains 1040 amino acids and mouse RAG-2 contains 527 amino acids. The enzymatic activity of the RAG proteins is largely concentrated in a core region; residues 384–1008 of RAG-1 and residues 1–387 of RAG-2 retain most of the DNA cleavage activity. The RAG-1 core contains three acidic residues (D600, D708, and E962) in what is called the DDE motif, the major active site for DNA cleavage. These residues are critical for nicking the DNA strand and for forming the DNA hairpin. Residues 384–454 of RAG-1 comprise a nonamer-binding region (NBR) that specifically binds the conserved nonomer (9 nucleotides) of the RSS and the central domain (amino acids 528–760) of RAG-1 binds specifically to the RSS heptamer. The core region of RAG-2 is predicted to form a six-bladed beta-propeller structure that appears less specific than RAG-1 for its target.