Cell response after SARS-CoV-2 Induced DNA damage
Medical Review (Med. pregled), 2024, 60(1), 5-9.
T. Valkov1,2, G. Dimitrov3,4, R. Argirova5
1 Specialized Hospital for Active Treatment of Infectious and Parasitic Diseases „Prof. Ivan Kirov“, Sofia
2 Department of Infectious Diseases, Parasitology and Tropical Medicine, Faculty of Medicine, Medical University – Sofia
3 University Multiprofile Hospital for Active Treatment “Tsaritsa Yoanna–ISUL”, Sofia
4 Department of Medical Oncology, Faculty of Medicine, Medical University, Sofia
5 Clinical Laboratory, Tokuda Hospital, Sofia
Abstract. SARS-CoV-2 is a RNA virus, a causative agent of COVID-19 and responsible for the current pandemic [1]. A lot of reports declare the virus implication in a range of intracellular signaling, but the effect on cell DNA integrity and the mechanisms of its maintenance remain unknown. Data demonstrates that SARS-CoV-2 infection induces damages in cell DNA and influences the mechanisms for DNA repair. Viral proteins ORF6 and NSP13 stimulate degradation of checkpoint kinase 1 (CHK1) participating in DNA repair process in proteasome or by autophagy. The loss of CHK1 decreases cell dNTP concentration, so hindering the transition to S-phase of cell division, results in accumulation of errors in DNA transcription, activation of proinflammatory signaling and cell damage. Another viral protein – N-SARS-CoV-2, inhibits the regulatory function of р53-Binding Protein 1 (р53ВР1) competing with it for joining to damage-induced long non-coding RNAs (dilncRNAs), synthesized during DNA damage and marking it. Thus, DNA repair processes are affected. The aim of current paper is to review some details of pathogenetic mechanisms linked to cell genome integrity during SARS-CoV-2 infection. The processes affecting cell cycle division and accompanying errors in DNA transcription, as well as the mechanisms hampering DNA repair, will be also described.
Key words: SARS-CoV-2 infection, DNA-repair, proinflammatory response
Address for correspondence: Prof. Radka Argirova, MD, DMedSc, e-mail: radkaargirova@abv.bg