The joining of V and J gene segments creates antibody diversity.
ABSTRACT The variable regions of mouse kappa (kappa) chains are coded for by multiple variable (V) gene segments and multiple joining (J) gene segments. The V kappa gene segments code for residues 1 to 95; the J kappa gene segments code for residues 96 to 108 (refs 1-3). This gene organisation is similar to that encoding the V lambda regions. Diversity in V kappa regions arises from several sources: (1) there are multiple germ-line V kappa gene segments and J kappa gene segments; (2) combinatorial joining of V kappa gene segments with different germline J kappa gene segments; and possibly, (3) somatic point mutation, as postulated for V lambda gene segments. Also, from a comparison of the number of germ-line J kappa gene segments and amino acid sequences, it has been suggested that J kappa region sequences may be determined by the way V kappa and J kappa gene segments are joined. This report supports this model by directly associating various J kappa sequences with given J kappa gene segments.
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ABSTRACT: Nonhomologous end joining (NHEJ) can effectively resolve chromosome breaks despite diverse end structures; however, it is unclear how the steps employed for resolution are determined. We sought to address this question by analysing cellular NHEJ of ends with systematically mispaired and damaged termini. We show NHEJ is uniquely proficient at bypassing subtle terminal mispairs and radiomimetic damage by direct ligation. Nevertheless, bypass ability varies widely, with increases in mispair severity gradually reducing bypass products from 85 to 6%. End-processing by nucleases and polymerases is increased to compensate, although paths with the fewest number of steps to generate a substrate suitable for ligation are favoured. Thus, both the frequency and nature of end processing are tailored to meet the needs of the ligation step. We propose a model where the ligase organizes all steps during NHEJ within the stable paired-end complex to limit end processing and associated errors.Nature Communications 07/2014; 5:4286. DOI:10.1038/ncomms5286 · 10.74 Impact Factor
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ABSTRACT: Neither the horse, nor the elephant, definitely not the tiger, but the weak and defenceless lamb is chosen for sacrifice - states a sanskrit observation coined about 1500 years ago (adjacent page). The ability to defend oneself against external and internal aggressors is indispensable for survival. Some form of selfdefence is a basic requirement needed to protect oneself from a world of pathogens that is forever evolving. In mammals, the body's defence system is highly evolved. In them, the non-specific innate immune system and the specific adaptive immune system are linked together to form a formidable integrated host defence mechanism.Erkenntnis 01/1995;
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ABSTRACT: IgG Sac is an immunoglobulin with large deletions in both heavy and light chains. Reexamination of the amino acid sequence of the γ chains of this immunoglobulin has led to the conclusion that the deletion in these chains, like that in the light chains, is the result of a pre-translational event, and not the result of in vivo proteolytic degradation. These chains differ from other γ heavy chain disease proteins in that the post-deletion normal sequence begins with the J segment rather than with the hinge region, and in that they are covalently associated with light chains.Molecular Immunology 04/1981; 18(3-18):257-259. DOI:10.1016/0161-5890(81)90093-6 · 3.00 Impact Factor