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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, Nudelman, German, Panchenko, Anna R., Cooper, David N. and Pavlov, Youri I. 2018. DNA polymerase η mutational signatures are found in a variety of different types of cancer. Cell Cycle 17 (3) , pp. 348-355. 10.1080/15384101.2017.1404208

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
ISSN: 1538-4101
Date of First Compliant Deposit: 7 December 2017
Date of Acceptance: 15 November 2017
Last Modified: 29 Jun 2019 15:16

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