'Role of non-homologous end joining in V(D)J recombination'. ^ Malu, Shruti Malshetty, Vidyasagar Francis, Dailia Cortes, Patricia (2012).'Repair of Double-Strand DNA Breaks by the Human Nonhomologous DNA End Joining Pathway: the Iterative Processing Model'. ^ Ma, Yunmei Lu, Haihui Schwarz, Klaus Lieber, Michael (September 2005). 'Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis'. 'The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus'. ^ Matsuda, F Ishii, K Bourvagnet, P Kuma, K Hayashida, H Miyata, T Honjo, T (1998).^ 'The Nobel Prize in Physiology or Medicine 1987'.V(D)J recombination is therefore a very costly process that must be (and is) strictly regulated and controlled. If the resulting sequence is out-of-frame, the development of the cell will be arrested, and the cell will not survive to maturity. However, a major caveat to this process is that the DNA sequence must remain in-frame in order to maintain the correct amino acid sequence in the final protein product. V(D)J recombination allows for the generation of immunoglobulins and T cell receptors to antigens that neither the organism nor its ancestor(s) need to have previously encountered, allowing for an adaptive immune response to novel pathogens that develop or to those that frequently change ( e.g., seasonal influenza). Process Īll of these processing events result in an antigen-binding region that is highly variable, even when the same gene segments are recombined. This is an important feature in the regulation of V(D)J recombination. Following what is known as the 12/23 Rule, gene segments to be recombined are usually adjacent to RSSs of different spacer lengths ( i.e., one has a '12RSS' and one has a '23RSS'). The length of the spacer region corresponds to approximately one (12 basepairs) or two turns (23 basepairs) of the DNA helix. While the majority of RSSs vary in sequence, the consensus heptamer and nonamer sequences are CACAGTG and ACAAAAACC, respectively and although the sequence of the spacer region is poorly conserved, the length is highly conserved. RSSs are composed of three elements: a heptamer of seven conserved nucleotides, a spacer region of 12 or 23 basepairs in length, and a nonamer of nine conserved nucleotides. To maintain the specificity of recombination, V(D)J recombinase recognizes and binds to Recombination Signal Sequences (RSSs) flanking the variable (V), diversity (D), and joining (J) genes segments.
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