A Backup Role of DNA Polymerase κ in Ig Gene Hypermutation Only Takes Place in the Complete Absence of DNA Polymerase η
| العنوان: | A Backup Role of DNA Polymerase κ in Ig Gene Hypermutation Only Takes Place in the Complete Absence of DNA Polymerase η |
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| المؤلفون: | Sandra K. Weller, Alain Sarasin, Anne Stary, Claude-Agnès Reynaud, Jean-Claude Weill, Frédéric Delbos, Said Aoufouchi, Ahmad Faili |
| المصدر: | The Journal of Immunology. 182:6353-6359 |
| بيانات النشر: | The American Association of Immunologists, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, Xeroderma pigmentosum, DNA polymerase, DNA Mutational Analysis, Immunology, Somatic hypermutation, DNA-Directed DNA Polymerase, medicine.disease_cause, Mice, Exon, medicine, Animals, Humans, Immunology and Allergy, RNA, Messenger, Polymerase, Mice, Knockout, B-Lymphocytes, Xeroderma Pigmentosum, Mutation, Splice site mutation, biology, Reverse Transcriptase Polymerase Chain Reaction, Mutagenesis, medicine.disease, Molecular biology, biology.protein, Female, Somatic Hypermutation, Immunoglobulin |
| الوصف: | Patients with the variant form of xeroderma pigmentosum (XPV) syndrome have a genetic deficiency in DNA polymerase (Pol) η, and display accordingly an increased skin sensitivity to UV light, as well as an altered mutation pattern of their Ig V genes in memory B cells, alteration that consists in a reduced mutagenesis at A/T bases. We previously suggested that another polymerase with a different mutation signature, Pol κ, is used as backup for Ig gene hypermutation in both humans and mice in cases of complete Pol η deficiency, a proposition supported in this study by the analysis of Pol η × Pol κ double-deficient mice. We also describe a new XPV case, in which a splice site mutation of the first noncoding exon results in a decreased mRNA expression, a mRNA that otherwise encodes a normal Pol η protein. Whereas the Pol η mRNA level observed in patient’s fibroblasts is one-twentieth the value of healthy controls, it is only reduced to one-fourth of the normal level in activated B cells. Memory B cells from this patient showed a 50% reduction in A/T mutations, with a spectrum that still displays a strict Pol η signature. Pol η thus appears as a dominant enzyme in hypermutation, its presence precluding the use of a substitute enzyme even in conditions of reduced availability. Such a dominant behavior may explain the lack of Pol κ signature in Ig gene mutations of some XPV patients previously described, for whom residual Pol η activity might exist. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b861cb2235c533e7025959405198e2d5Test https://doi.org/10.4049/jimmunol.0900177Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b861cb2235c533e7025959405198e2d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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