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. ORCID: https://orcid.org/0000-0002-8943-8484 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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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.

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:	21 Nov 2024 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/107435

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