Junctional diversity
Junctional diversitydescribes theDNAsequence variations introduced by the improper joining ofgenesegments during the process ofV(D)J recombination.This process of V(D)J recombination has vital roles for thevertebrateimmune system,as it is able to generate a huge repertoire of differentT-cell receptor(TCR) andimmunoglobulinmolecules required forpathogenantigenrecognition by T-cells and B cells, respectively.
Process[edit]
Junctional diversity includes the process of somatic recombination orV(D)J recombination,during which the different variable gene segments (those segments involved in antigen recognition) of TCRs and immunoglobulins are rearranged and unused segments removed. This introducesdouble-strand breaksbetween the required segments. These ends form hairpin loops and must be joined together to form a single strand (summarised in diagram, right). This joining is a very inaccurate process that results in the variable addition or subtraction ofnucleotidesand, thus, generates junctional diversity.[1]
Generation of junctional diversity starts as the proteins,recombination activating gene-1 and -2 (RAG1 and RAG2), along with DNA repair proteins, such asArtemis,[2]are responsible for single-stranded cleavage of the hairpin loops and addition of a series ofpalindromic,'P' nucleotides. Subsequent to this, the enzyme,terminal deoxynucleotidyl transferase(TdT), adds further random 'N' nucleotides. The newly synthesised strands anneal to one another, but mismatches are common.Exonucleasesremove these unpaired nucleotides and the gaps are filled byDNA synthesisandrepairmachinery.[1][3]Exonucleases may also cause shortening of this junction, however this process is still poorly understood.[4]
Junctional diversity is liable to causeframe-shift mutationsand thus production of non-functional proteins. Therefore, there is considerable waste involved in this process.[1]
References[edit]
- ^abcJaneway, C.A., Travers, P., Walport, M., Shlomchik, M.J. (2005).Immunology(6th ed.). Garland Science.
{{cite book}}:CS1 maint: multiple names: authors list (link) - ^Ma, Y., Pannicke, U., Schwarz, K., Lieber, M.R. (2004)."Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination".Cell.108(6): 781–794.doi:10.1016/S0092-8674(02)00671-2.PMID11955432.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^Wyman, C., Kanaar, R. (2006). "DNA double-strand break repair: All's well that ends well".Annual Review of Genetics.40:363–383.doi:10.1146/annurev.genet.40.110405.090451.PMID16895466.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^Krangel, M.S. (2009)."Mechanics of T cell receptor gene rearrangement".Current Opinion in Immunology.21(2): 133–139.doi:10.1016/j.coi.2009.03.009.PMC2676214.PMID19362456.