SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence.
SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence.
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SARS-COV-2感染通过CHK1降解和53BP1募集和细胞衰老引起DNA损伤。
DOI：
10.1038/s41556-023-01096-x
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发表时间：
2023-04
影响因子：
21.3
通讯作者：
di Fagagna, Fabrizio d'Adda
中科院分区：
文献类型：
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作者：
Gioia, Ubaldo;Tavella, Sara;Martinez-Orellana, Pamela;Cicio, Giada;Colliva, Andrea;Ceccon, Marta;Cabrini, Matteo;Henriques, Ana C.;Fumagalli, Valeria;Paldino, Alessia;Presot, Ettore;Rajasekharan, Sreejith;Iacomino, Nicola;Pisati, Federica;Matti, Valentina;Sepe, Sara;Conte, Matilde I.;Barozzi, Sara;Lavagnino, Zeno;Carletti, Tea;Volpe, Maria Concetta;Cavalcante, Paola;Iannacone, Matteo;Rampazzo, Chiara;Bussani, Rossana;Tripodo, Claudio;Zacchigna, Serena;Marcello, Alessandro;di Fagagna, Fabrizio d'Adda
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是导致2019冠状病毒病（COVID-19）大流行的RNA病毒。尽管SARS-CoV-2被报道改变了几种细胞途径，但其对DNA完整性的影响及其机制仍不清楚。在这里，我们表明，SARS-CoV-2引起DNA损伤和electin改变DNA损伤反应。SARS-CoV-2蛋白ORF 6和NSP 13分别通过蛋白酶体和自噬降解DNA损伤反应激酶CHK 1。CHK 1缺失导致脱氧核苷三磷酸（dNTP）不足，导致S期进展受损、DNA损伤、促炎途径激活和细胞衰老。补充脱氧核苷可以降低这种情况。此外，SARS-CoV-2 N蛋白通过干扰损伤诱导的长非编码RNA来损害53 BP 1的局部募集，从而减少DNA修复。在SARS-CoV-2感染的小鼠和COVID-19患者中重现了关键观察结果。我们认为，SARS-CoV-2通过提高核糖核苷三磷酸水平以促进其复制，并以dNTPs为代价，通过劫持损伤诱导的长非编码RNA的生物学，威胁基因组的完整性，并导致改变的DNA损伤反应激活，诱导炎症和细胞衰老。Gioia，Tavella等人表明，严重急性呼吸综合征冠状病毒2通过CHK 1降解引起DNA损伤，并损害53 BP 1向DNA损伤的募集。诱导的DNA损伤与促炎细胞因子和衰老标志物的表达相关。
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 non-coding RNAs, thus reducing DNA repair. Key observations are recapitulated in SARS-CoV-2-infected mice and patients with COVID-19. We propose that SARS-CoV-2, by boosting ribonucleoside triphosphate levels to promote its replication at the expense of dNTPs and by hijacking damage-induced long non-coding RNAs’ biology, threatens genome integrity and causes altered DNA damage response activation, induction of inflammation and cellular senescence. Gioia, Tavella et al. show that severe acute respiratory syndrome coronavirus 2 causes DNA damage through CHK1 degradation and impairs 53BP1 recruitment to DNA lesions. The induced DNA damage is associated with expression of pro-inflammatory cytokines and senescence markers.
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影响因子：
24.8
作者：
Fumagalli, Valeria;Rava, Micol;Marotta, Davide;Di Lucia, Pietro;Laura, Chiara;Sala, Eleonora;Grillo, Marta;Bono, Elisa;Giustini, Leonardo;Perucchini, Chiara;Mainetti, Marta;Sessa, Alessandro;Garcia-Manteiga, Jose M.;Donnici, Lorena;Manganaro, Lara;Delbue, Serena;Broccoli, Vania;De Francesco, Raffaele;D'Adamo, Patrizia;Kuka, Mirela;Guidotti, Luca G.;Iannacone, Matteo
通讯作者：
Iannacone, Matteo
影响因子：
4.6
作者：
Ahmadi A;Moradi S
通讯作者：
Moradi S
DOI：
10.1038/s41579-018-0003-6
发表时间：
2018-06
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Choi Y;Bowman JW;Jung JU
通讯作者：
Jung JU
影响因子：
8.8
作者：
Garcia G Jr;Sharma A;Ramaiah A;Sen C;Purkayastha A;Kohn DB;Parcells MS;Beck S;Kim H;Bakowski MA;Kirkpatrick MG;Riva L;Wolff KC;Han B;Yuen C;Ulmert D;Purbey PK;Scumpia P;Beutler N;Rogers TF;Chatterjee AK;Gabriel G;Bartenschlager R;Gomperts B;Svendsen CN;Betz UAK;Damoiseaux RD;Arumugaswami V
通讯作者：
Arumugaswami V
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J