DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination.Report as inadecuate




DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Développement du Systeme Immunitaire 2 Immuno-Hématologie et Immunopathologie 3 ERIGC - Etude des relations instabilité génétique et cancer

Abstract : Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination CSR. These mutations are dependent upon activation-induced cytidine deaminase AID and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant XP-V syndrome who are deficient in DNA polymerase eta pol eta, that this enzyme could be responsible for a large part of the mutations occurring on A-T bases. Here we show, by analyzing switched memory B cells from two XP-V patients, that pol eta is also an A-T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.





Author: Ahmad Faili - Said Aoufouchi - Sandra Weller - Françoise Vuillier - Anne Stary - Alain Sarasin - Claude-Agnès Reynaud - Jean-Cl

Source: https://hal.archives-ouvertes.fr/



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