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

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

Research output: Contribution to journalArticle

Abstract

To determine whether DNA polymerase η 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 η 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 η 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.

Original languageEnglish (US)
Pages (from-to)537-541
Number of pages5
JournalNature Immunology
Volume2
Issue number6
DOIs
StatePublished - Jun 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zeng, X., Winter, D. B., Kasmer, C., Kraemer, K. H., Lehmann, A. R., & Gearhart, P. J. (2001). DNA polymerase η is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. Nature Immunology, 2(6), 537-541. https://doi.org/10.1038/88740