Somatic mutation hotspots correlate with DNA polymerase η error spectrum

Igor B. Rogozin, Youri I. Pavlov, Katarzyna Bebenek, Toshiro Matsuda, Thomas A. Kunkel

Research output: Contribution to journalArticlepeer-review

268 Scopus citations

Abstract

Mutational spectra analysis of 15 immunoglobulin genes suggested that consensus motifs RGYW and WA were universal descriptors of somatic hypermutation. Highly mutable sites, "hotspots", that matched WA were preferentially found in one DNA strand and RGYW hotspots were found in both strands. Analysis of base-substitution hotspots in DNA polymerase error spectra showed that 33 of 36 hotspots in the human polymerase η spectrum conformed to the WA consensus. This and four other characteristics of polymerase η substitution specificity suggest that errors introduced by this enzyme during synthesis of the nontranscribed DNA strand in variable regions may contribute to strand-specific somatic hypermutagenesis of immunoglobulin genes at A-T base pairs.

Original languageEnglish (US)
Pages (from-to)530-536
Number of pages7
JournalNature Immunology
Volume2
Issue number6
DOIs
StatePublished - Jun 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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