DNA polymerase η mutational signatures are found in a variety of different types of cancer

Igor B. Rogozin, Alexander Goncearenco, Artem G. Lada, Subhajyoti De, Vyacheslav Yurchenko, German Nudelman, Anna R. Panchenko, David N. Cooper, Youri I. Pavlov

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

DNA polymerase (pol) η is a specialized error-prone polymerase with at least two quite different and contrasting cellular roles: to mitigate the genetic consequences of solar UV irradiation, and promote somatic hypermutation in the variable regions of immunoglobulin genes. Misregulation and mistargeting of pol η can compromise genome integrity. We explored whether the mutational signature of pol η could be found in datasets of human somatic mutations derived from normal and cancer cells. A substantial excess of single and tandem somatic mutations within known pol η mutable motifs was noted in skin cancer as well as in many other types of human cancer, suggesting that somatic mutations in A:T bases generated by DNA polymerase η are a common feature of tumorigenesis. Another peculiarity of pol ηmutational signatures, mutations in YCG motifs, led us to speculate that error-prone DNA synthesis opposite methylated CpG dinucleotides by misregulated pol η in tumors might constitute an additional mechanism of cytosine demethylation in this hypermutable dinucleotide.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalCell Cycle
Volume17
Issue number3
DOIs
StatePublished - Feb 1 2018

Keywords

  • DNA lesion bypass
  • Hypermutation
  • POLH
  • gene expression profiles
  • mutable motif
  • skin cancer
  • sloppy DNA polymerase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Rogozin, I. B., Goncearenco, A., Lada, A. G., De, S., Yurchenko, V., Nudelman, G., Panchenko, A. R., Cooper, D. N., & Pavlov, Y. I. (2018). DNA polymerase η mutational signatures are found in a variety of different types of cancer. Cell Cycle, 17(3), 348-355. https://doi.org/10.1080/15384101.2017.1404208