Merkel Cell Polyomavirus and DNA Damage Response
- 1Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
- 2Department of Medical Biology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9019 Tromsø, Norway
Abstract
Cellular DNA is constantly exposed to endogenous and exogenous genotoxic factors causing mutations. Therefore, safeguarding the integrity of the human genome is a conditio sine qua non for normal cell function. To maintain genomic integrity, complex multiprotein networks, known as DNA damage response (DDR) signaling pathways, sense DNA lesions and repair mistakes or induce cell death when extensive unrepairable damage has occurred. Two of the major DDR pathways are the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) cascades. The ATM pathway primarily responds to double-strand breaks, whereas the ATR cascade is activated by single-stranded DNA and mediates the response to replication stress. One of the exogenous factors that can induce DNA aberrations and trigger the ATM and ATR pathways is viral infection. This review focuses on current knowledge regarding the interaction between Merkel cell polyomavirus, a major etiological risk factor of Merkel cell carcinoma, and the ATM and ATR pathways and the effect on viral replication and virus-induced oncogenesis. The review elaborates on the role of the viral oncoproteins large T antigen and small t antigen in DDR interaction. Possible therapies targeting DDR in Merkel cell carcinoma and gaps in understanding the molecular mechanisms of Merkel cell polyomavirus-triggered ATM and ATR pathway activation are discussed.
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BibTeX
@article{passerini2026merkel,
title = {{Merkel Cell Polyomavirus and DNA Damage Response}},
author = {Sara Passerini and Sara Messina and Ugo Moens and Valeria Pietropaolo},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198881},
url = {https://www.mdpi.com/1422-0067/27/19/8881},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Merkel Cell Polyomavirus and DNA Damage Response
AU - Sara Passerini
AU - Sara Messina
AU - Ugo Moens
AU - Valeria Pietropaolo
PY - 2026
DA - 2026/10/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198881
UR - https://www.mdpi.com/1422-0067/27/19/8881
AB - Cellular DNA is constantly exposed to endogenous and exogenous genotoxic factors causing mutations. Therefore, safeguarding the integrity of the human genome is a conditio sine qua non for normal cell function. To maintain genomic integrity, complex multiprotein networks, known as DNA damage response (DDR) signaling pathways, sense DNA lesions and repair mistakes or induce cell death when extensive unrepairable damage has occurred. Two of the major DDR pathways are the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) cascades. The ATM pathway primarily responds to double-strand breaks, whereas the ATR cascade is activated by single-stranded DNA and mediates the response to replication stress. One of the exogenous factors that can induce DNA aberrations and trigger the ATM and ATR pathways is viral infection. This review focuses on current knowledge regarding the interaction between Merkel cell polyomavirus, a major etiological risk factor of Merkel cell carcinoma, and the ATM and ATR pathways and the effect on viral replication and virus-induced oncogenesis. The review elaborates on the role of the viral oncoproteins large T antigen and small t antigen in DDR interaction. Possible therapies targeting DDR in Merkel cell carcinoma and gaps in understanding the molecular mechanisms of Merkel cell polyomavirus-triggered ATM and ATR pathway activation are discussed.
SN - 1422-0067
ER -