Targeting of Somatic Hypermutation to Immunoglobulin Genes

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  • Targeting of Somatic Hypermutation to Immunoglobulin Genes Book Detail

  • Author : Atsushi Tanaka
  • Release Date : 2009
  • Publisher :
  • Genre :
  • Pages : 129
  • ISBN 13 : 9781109314090
  • File Size : 15,15 MB

Targeting of Somatic Hypermutation to Immunoglobulin Genes by Atsushi Tanaka PDF Summary

Book Description: Another regulatory mechanism governing the specific targeting of SHM is the distribution of mutations within Ig genes. In Ig genes, mutations occur about 100 nucleotides downstream of the transcription start and extend to 1-2kb, thereby targeting regions containing rearranged V(D)J gene segments and sparing constant regions. To understand whether uracils resulting from AID activity are faithfully repaired in the very 5' unmutated region, or whether AID does not access or does not act in the 5' region, the distribution of mutations was compared between uracil DNA glycosylase (Ung)-deficient and wild-type mice in endogenous Ig genes and in a hypermutable Ig transgene. If AID gains access to the 5' region which is unmutated in wild-type mice, one would expect an "AID footprint," namely transition mutations from C and G in Ung-deficient mice in the region normally devoid of SHM. The results indicate that the distribution of total mutations and transitions from C and G is indistinguishable in wild-type and Ung-deficient mice. To confirm the finding, Ig genes from mice deficient in both Ung and MSH6 were analyzed and the mutation distributions were also indistinguishable from the wild-type. Thus, AID does not gain access to or cannot act at the 5' region of Ig genes.

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