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Hypothesis: A biological role for germline transcription in the mechanism of V(D)J recombination - implications for initiation of allelic exclusion

Franklin, Andrew

Description

The sequences that encode the antigen-binding sites of IgH and IgL chains - variable (V), diversity (D, H chain loci only) and joining (J) sequences - are configured as separate DNA segments at the germline level. Expression of an Ig molecule requires V(D)J assembly. Productive V(D)J recombination is monoallelic. How rearrangement is initiated differentially at maternal and paternal alleles is unclear. The products of recombination activating gene (RAG)1 and RAG2 mediate rearrangement by...[Show more]

dc.contributor.authorFranklin, Andrew
dc.date.accessioned2015-12-13T23:03:45Z
dc.identifier.issn0818-9641
dc.identifier.urihttp://hdl.handle.net/1885/85063
dc.description.abstractThe sequences that encode the antigen-binding sites of IgH and IgL chains - variable (V), diversity (D, H chain loci only) and joining (J) sequences - are configured as separate DNA segments at the germline level. Expression of an Ig molecule requires V(D)J assembly. Productive V(D)J recombination is monoallelic. How rearrangement is initiated differentially at maternal and paternal alleles is unclear. The products of recombination activating gene (RAG)1 and RAG2 mediate rearrangement by cleaving the DNA between an unrearranged gene segment and adjacent recombination signal sequences (RSS). It is proposed that supercoiling generated during germline transcription at Ig loci (which occurs concomitantly with rearrangement) is required at RSS for RAG1/2 recognition. Rearrangement might hence initiate sequentially at maternal and paternal alleles where deregulated germline transcription causes RAG1/2 recognition of RSS to become stochastic.
dc.publisherBlackwell Publishing Ltd
dc.sourceImmunology and Cell Biology
dc.subjectKeywords: DNA; immunoglobulin heavy chain; immunoglobulin light chain; RAG1 protein; RAG2 protein; allele; animal cell; article; B lymphocyte; controlled study; DNA determination; gene expression; gene sequence; genetic code; genetic transcription; genetic variabil Allelic exclusion; Germline transcription; Recombination activating gene; Recombination signal sequence; V(D)J recombination
dc.titleHypothesis: A biological role for germline transcription in the mechanism of V(D)J recombination - implications for initiation of allelic exclusion
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume84
dc.date.issued2006
local.identifier.absfor060406 - Genetic Immunology
local.identifier.ariespublicationMigratedxPub13263
local.type.statusPublished Version
local.contributor.affiliationFranklin, Andrew, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage396
local.bibliographicCitation.lastpage403
local.identifier.doi10.1111/j.1440-1711.2006.01437.x
dc.date.updated2015-12-12T07:50:59Z
local.identifier.scopusID2-s2.0-33745079671
CollectionsANU Research Publications

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