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.

doi:10.1038/88740

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

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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Signature 9 is a mutation pattern attributed to pol η recruited to repair AID-damaged DNA during somatic hypermutation in immunoglobulin genes.
“is characterized by a pattern of mutations that has been attributed to pol h (see the Discussion section for details) recruited for the repair of DNA damaged by AID during somatic hypermutation in immunoglobulin genes [28][29][30] .”
From DNA polymerase η mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [30]

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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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