作者
Ubaldo Gioia, Sara Tavella, Pamela Martínez-Orellana, Giada Cicio, Andrea Colliva, Marta Ceccon, Matteo Cabrini, Ana C Henriques, Valeria Fumagalli, Alessia Paldino, Ettore Presot, Sreejith Rajasekharan, Nicola Iacomino, Federica Pisati, Valentina Matti, Sara Sepe, Matilde I Conte, Sara Barozzi, Zeno Lavagnino, Tea Carletti, Maria Concetta Volpe, Paola Cavalcante, Matteo Iannacone, Chiara Rampazzo, Rossana Bussani, Claudio Tripodo, Serena Zacchigna, Alessandro Marcello, Fabrizio d’Adda di Fagagna
发表日期
2023/4
期刊
Nature Cell Biology
卷号
25
期号
4
页码范围
550-564
出版商
Nature Publishing Group UK
简介
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively. CHK1 loss leads to deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, DNA damage, pro-inflammatory pathways activation and cellular senescence. Supplementation of deoxynucleosides reduces that. Furthermore, SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long …
学术搜索中的文章
U Gioia, S Tavella, P Martínez-Orellana, G Cicio… - Nature Cell Biology, 2023