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Cited by 120DNA Repair MechanismsDNA and Nucleic Acid ChemistryRNA regulation and disease

Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase η during copying of a mouse immunoglobulin κ light chain transgene

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Pavlov, Youri I., Rogozin, Igor B., Galkin, Alexey P., Aksenova, Anna Y., Hanaoka, Fumio, Rada, Christina, Kunkel, Thomas A.·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.152126799PMC PMC126606
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Abstract

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. The in vitro and in vivo base 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 observed in vivo were also found in spectra generated by mouse pol η in 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 generated in 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.

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Authors
Pavlov, Y. I., Rogozin, I. B., Galkin, A. P., Aksenova, A. Y., Hanaoka, F., Rada, C., & Kunkel, T. A.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-07-15
Volume
99
Issue
15
Pages
9954-9959
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.152126799
PMC
PMC126606
OpenAlex
W2066181706
Cited by
120
References
51
Citations by year
2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 3 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 1
FWCI
4.95
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
somatic hypermutation, DNA polymerase eta, immunoglobulin kappa light chain, mutational hotspots, transcribed strand, transgenes
MeSH terms
Y-Family DNA Polymerases, Adenine, Animals, Base Sequence, DNA-Directed DNA Polymerase, Genetic Techniques, Immunoglobulin kappa-Chains, Mice, Transgenic, Molecular Sequence Data, Monte Carlo Method, Thymine, Transcription, Genetic, Transgenes, Base Pairing, Somatic Hypermutation, Immunoglobulin, Mice

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