Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene
| Autor: | Thomas A. Kunkel, Youri I. Pavlov, Alexey P. Galkin, Anna Y. Aksenova, Igor B. Rogozin, Christina Rada, Fumio Hanaoka |
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| Rok vydání: | 2002 |
| Předmět: |
Transcription
Genetic DNA polymerase Base pair Molecular Sequence Data Somatic hypermutation Mice Transgenic DNA-Directed DNA Polymerase Immunoglobulin light chain chemistry.chemical_compound Immunoglobulin kappa-Chains Mice Animals Transgenes Gene Base Pairing Genetics Multidisciplinary biology DNA synthesis Base Sequence Point mutation Adenine Biological Sciences Molecular biology Thymine chemistry Genetic Techniques biology.protein Somatic Hypermutation Immunoglobulin Monte Carlo Method |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 99(15) |
| ISSN: | 0027-8424 |
| Popis: | To test the hypothesis that inaccurate DNA synthesis by mammalian DNA polymerase η (pol η) contributes to somatic hypermutation (SHM) of Ig genes, we measured the error specificity of mouse pol η during synthesis of each strand of a mouse Ig κ light chain transgene. We then compared the results to the base substitution specificity of SHM of this same gene in the mouse. Thein vitroandin vivobase substitution spectra shared a number of common features. A highly significant correlation was observed for overall substitutions at A-T pairs but not for substitutions at G-C pairs. Sixteen mutational hotspots at A-T pairs observedin vivowere also found in spectra generated by mouse pol ηin vitro. The correlation was strongest for errors made by pol η during synthesis of the non-transcribed strand, but it was also observed for synthesis of the transcribed strand. These facts, and the distribution of substitutions generatedin vivo, support the hypothesis that pol η contributes to SHM of Ig genes at A-T pairs via short patches of low fidelity DNA synthesis of both strands, but with a preference for the non-transcribed strand. |
| Databáze: | OpenAIRE |
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