Cited by 420DNA Repair MechanismsT-cell and B-cell ImmunologyRNA regulation and disease

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DNA polymerase η is an A-T mutator in somatic hypermutation of immunoglobulin variable genes

Zeng, Xianmin, Winter, David B., Kasmer, Cynthia, Kraemer, Kenneth H., Lehmann, Alan R., Gearhart, Patricia J.·2001·Nature Immunology

DOI 10.1038/88740

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Abstract

To determine whether DNA polymerase eta plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable VH6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase eta had genetic defects. The frequency of mutation was normal but the types of base changes were different: there was a decrease in mutations at A and T and a concomitant rise in mutations at G and C. We propose that more than one polymerase contributes to hypermutation and that if one is absent, others compensate. The data indicate that polymerase eta is involved in generating errors that occur predominantly at A and T and that another polymerase(s) may preferentially generate errors opposite G and C.

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Wood, R. D., Gearhart, P. J. & Neuberger, M. S. Hypermutation in antibody genes. Phil. Trans. R. Soc. Lond. B 356, 1–125 (2001).

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Mutating for Good: DNA Damage Responses During Somatic Hypermutation
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Background
Hyper‐immunoglobulin M syndromes caused by intrinsic B‐lymphocyte defects
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Background
Increased Susceptibility to UV-Induced Skin Carcinogenesis in Polymerase η–deficient Mice
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“This hypothesis has been supported by error specificity studies during copying of immunoglobulin gene-coding sequences in vitro (22) and by studies showing that mutations at A-T base pairs in immunoglobulin genes are underrepresented in XPV patients (23, 24 ).”
BackgroundResultInfluential
Mutator phenotypes due to DNA replication infidelity
Arana, M. E., & Kunkel, T. A. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.10.003 · Cited by 103
Examination of Msh6- and Msh3-deficient Mice in Class Switching Reveals Overlapping and Distinct Roles of MutS Homologues in Antibody Diversification
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Background
Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations
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Inhibition of mutagenic translesion synthesis: A possible strategy for improving chemotherapy?
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Background
Mutational fingerprints of aging
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Background
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Authors: Zeng, X., Winter, D. B., Kasmer, C., Kraemer, K. H., Lehmann, A. R., & Gearhart, P. J.
Affiliations: National Institutes of Health (US)
Walter Reed Army Institute of Research (US)
University of Sussex (GB)
Corresponding author: Gearhart, Patricia J.
ORCID: Winter, David B.
Kraemer, Kenneth H.
Lehmann, Alan R.
Gearhart, Patricia J.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2001-06
Volume: 2
Issue: 6
Pages: 537-541
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/88740
OpenAlex: W1560486125
Semantic Scholar: 8a9d17ca74ddcb4e43d0ff02f4b768b9cb457829
Cited by: 420
References: 49
Citations by year: 2026: 1 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 12 · 2019: 12 · 2018: 10 · 2017: 10 · 2016: 11 · 2015: 8 · 2014: 12 · 2013: 15 · 2012: 15
FWCI: 13.73
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Cancer Institute (Z01BC004517)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: DNA polymerase eta, somatic hypermutation, immunoglobulin variable region genes, xeroderma pigmentosum variant, peripheral blood lymphocytes, error-prone mutagenesis
MeSH terms: Y-Family DNA Polymerases, Animals, B-Lymphocytes, Base Sequence, DNA, DNA-Directed DNA Polymerase, Genes, Immunoglobulin, Humans, Immunoglobulin Variable Region, Molecular Sequence Data, Mutation, Xeroderma Pigmentosum, Base Pairing, Mice

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DNA polymerase η is an A-T mutator in somatic hypermutation of immunoglobulin variable genes

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