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Cell Cycle. 2018;17(3):348-355. doi: 10.1080/15384101.2017.1404208. Epub 2018 Feb 15.

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

Author information

a National Center for Biotechnology Information, National Library of Medicine , National Institutes of Health , Bethesda , MD , USA.
b Department Microbiology and Molecular Genetics , University of California , Davis , CA , USA.
c Rutgers Cancer Institute of New Jersey , Rutgers University , New Brunswick , NJ , USA.
d Life Science Research Center , University of Ostrava, 71000 Ostrava , Czech Republic.
e Systems Biology Center , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , USA.
f Institute of Medical Genetics, School of Medicine , Cardiff University , UK.
g Eppley Institute for Research in Cancer and Allied Diseases , University of Nebraska Medical Center , Omaha , NE 68198, USA.
h Departments of Microbiology and Pathology , University of Nebraska Medical Center , Omaha , NE , USA.
i Biochemistry and Molecular Biology , University of Nebraska Medical Center , Omaha , NE , USA.
j Genetics, Cell Biology and Anatomy , University of Nebraska Medical Center , Omaha , NE , USA.


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.


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

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