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 Yurchenkod, German Nudelman, Anna R. Panchenko, David N. Cooper, Youri I Pavlov

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

DNA-Directed DNA Polymerase
Mutation
Neoplasms
Immunoglobulin Genes
Cytosine
Skin Neoplasms
Carcinogenesis
Genome
DNA

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

Cite this

Rogozin, I. B., Goncearenco, A., Lada, A. G., De, S., Yurchenkod, V., Nudelman, G., ... 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

DNA polymerase η mutational signatures are found in a variety of different types of cancer. / Rogozin, Igor B.; Goncearenco, Alexander; Lada, Artem G.; De, Subhajyoti; Yurchenkod, Vyacheslav; Nudelman, German; Panchenko, Anna R.; Cooper, David N.; Pavlov, Youri I.

In: Cell Cycle, Vol. 17, No. 3, 01.02.2018, p. 348-355.

Research output: Contribution to journalArticle

Rogozin, IB, Goncearenco, A, Lada, AG, De, S, Yurchenkod, V, Nudelman, G, Panchenko, AR, Cooper, DN & Pavlov, YI 2018, 'DNA polymerase η mutational signatures are found in a variety of different types of cancer', Cell Cycle, vol. 17, no. 3, pp. 348-355. https://doi.org/10.1080/15384101.2017.1404208
Rogozin IB, Goncearenco A, Lada AG, De S, Yurchenkod V, Nudelman G et al. DNA polymerase η mutational signatures are found in a variety of different types of cancer. Cell Cycle. 2018 Feb 1;17(3):348-355. https://doi.org/10.1080/15384101.2017.1404208
Rogozin, Igor B. ; Goncearenco, Alexander ; Lada, Artem G. ; De, Subhajyoti ; Yurchenkod, Vyacheslav ; Nudelman, German ; Panchenko, Anna R. ; Cooper, David N. ; Pavlov, Youri I. / DNA polymerase η mutational signatures are found in a variety of different types of cancer. In: Cell Cycle. 2018 ; Vol. 17, No. 3. pp. 348-355.
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