Effects of SARS-CoV-2 on DNA Damage Response Proteins Chk1 and P53: An in vitro Study

Authors

  • Mahmoud Ahmed Chawsheen Medical Research Centre, Hawler Medical University, Erbil, Kurdistan Region, Iraq; Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0000-0003-2277-1984
  • Hedy Ahmed Hassan Department of Physiotherapy, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan Region, Iraq https://orcid.org/0000-0002-4075-1189
  • Ahmed Abdulqader Al-Naqshbandi Department of Laboratory, Rizgary Teaching Hospital, Erbil, Kurdistan Region, Iraq https://orcid.org/0000-0002-0843-7958
  • Hawzheen Aziz Muhammad Branch of Basic Medical Sciences, College of Medicine, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq https://orcid.org/0000-0002-2066-1661
  • Mahmood Hawar Mahmood Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0000-0003-3010-2633
  • Agren Hamad Hamad Amin Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0009-0006-0768-024X
  • Botan Fattah Mina Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0009-0005-0958-5003
  • Chilar Mamand Hussein Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0009-0005-4957-1060
  • Sarwar Perot Muhammad Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0009-0009-2177-7517
  • Zhakaw Muhajir Hassan Department of General Sciences, Faculty of Education, Soran University, Erbil, Kurdistan Region, Iraq https://orcid.org/0009-0001-1099-2731

DOI:

https://doi.org/10.54133/ajms.v7i2.1513

Keywords:

Chk1, COVID-19, DNA damage, IgG, p53

Abstract

Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has had a global impact on millions of people's lives. Deteriorations in cellular activities induced by this lethal virus are not yet completely understood, and so its long-term consequences are unknown. There is increasing evidence that SARS-CoV-2 and its vaccinations may have a deleterious influence on DNA damage response (DDR)-associated proteins. Objective: To investigate the status of DNA integrity in COVID-19-recovered patients and post-recovered vaccinated individuals. Methods: Blood samples were taken from 88 participants who completed questionnaires and conducted face-to-face interviews. The samples were classified into four categories based on the subjects' PCR and vaccination status: PCR negative/not vaccinated, PCR positive/not vaccinated, PCR negative/vaccinated, and PCR positive/vaccinated. ELISA kits were used to determine the expression levels of TP53BP1, Chk1, and SARS-CoV-2 IgG proteins. Results: SARS-CoV-2 did not significantly reduce Chk1 expression, but it did have a significant negative influence on TP53BP1 expression when compared to the first group. Infection with SARS-CoV-2 and its vaccination resulted in increased Chk1 and IgG levels, as well as a significant increase in TP53BP1 expression compared to the second group. Conclusions: Both SARS-CoV-2 infection and the anti-SARS-CoV-2 vaccine may have a deleterious influence on DDR-associated proteins in vitro. Post-infection immunization may boost viral protection. While some studies imply that DDR effects are reversible, more research is needed to corroborate these assertions.

Downloads

Download data is not yet available.

References

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. DOI: https://doi.org/10.1038/s41586-020-2012-7

Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. PLoS Pathog. 2020;16(5):e1008536. doi: 10.1371/journal.ppat.1008536. DOI: https://doi.org/10.1371/journal.ppat.1008536

Sidiq K. Prevalence of COVID-19 and possible antigenic drifts in SARS-CoV-2 spike protein in Kurdistan region-Iraq. Passer J Basic Appl Sci. 2021;3(2):156-166. doi: 10.24271/psr.27 DOI: https://doi.org/10.24271/psr.27

Merad M, Vabret N. Highlights from a year in a pandemic. J Exp Med. 2021;218(5):e20210220. doi: 10.1084/jem.20210220. DOI: https://doi.org/10.1084/jem.20210220

Weitzman MD, Fradet-Turcotte A. Virus DNA Replication and the host DNA damage response. Annu Rev Virol. 2018;5(1):141-164. doi: 10.1146/annurev-virology-092917-043534. DOI: https://doi.org/10.1146/annurev-virology-092917-043534

Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG. Post-COVID-19 symptom burden: What is long-COVID and how should we manage it? Lung. 2021;199(2):113-119. doi: 10.1007/s00408-021-00423-z. DOI: https://doi.org/10.1007/s00408-021-00423-z

Xu LH, Huang M, Fang SG, Liu DX. Coronavirus infection induces DNA replication stress partly through interaction of its nonstructural protein 13 with the p125 subunit of DNA polymerase delta. J Biol Chem. 2011;286(45):39546-39559. doi: 10.1074/jbc.M111.242206. DOI: https://doi.org/10.1074/jbc.M111.242206

Yang J, Yu Y, Hamrick HE, Duerksen-Hughes PJ. ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis. 2003;24(10):1571-1580. doi: 10.1093/carcin/bgg137. DOI: https://doi.org/10.1093/carcin/bgg137

Cardozo CM, Hainaut P. Viral strategies for circumventing p53: the case of severe acute respiratory syndrome coronavirus. Curr Opin Oncol. 2021;33(2):149-158. doi: 10.1097/CCO.0000000000000713. DOI: https://doi.org/10.1097/CCO.0000000000000713

Wang X, Liu Y, Li K, Hao Z. Roles of p53-mediated host-virus interaction in coronavirus infection. Int J Mol Sci. 2023;24(7):6371. doi: 10.3390/ijms24076371. DOI: https://doi.org/10.3390/ijms24076371

Rasheed WS, Sarkees AN. IgG level of the third booster dose for mRNA of SARS-CoV-2 vaccines among Iraqi healthcare workers. Medicine (Baltimore). 2023;102(40):e35444. doi: 10.1097/MD.0000000000035444. DOI: https://doi.org/10.1097/MD.0000000000035444

Ebrahim F, Tabal S, Lamami Y, Alhudiri IM, El Meshri SE, Al Dwigen S, et al. Anti-SARS-CoV-2 IgG antibodies post-COVID-19 or post-vaccination in Libyan population: Comparison of four vaccines. Vaccines (Basel). 2022;10(12):2002-2022. doi: 10.3390/vaccines10122002. DOI: https://doi.org/10.3390/vaccines10122002

Flor N, Garcia MI, Molineri A, Bottasso O, Diez C, Veaute C. Antibodies to SARS-CoV2 induced by vaccination and infection correlate with protection against the infection. Vaccine. 2023;41(48):7206-7211. doi: 10.1016/j.vaccine.2023.10.038. DOI: https://doi.org/10.1016/j.vaccine.2023.10.038

Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141-154. doi: 10.1038/s41579-020-00459-7. DOI: https://doi.org/10.1038/s41579-020-00459-7

Victor J, Deutsch J, Whitaker A, Lamkin EN, March A, Zhou P, et al. SARS-CoV-2 triggers DNA damage response in Vero E6 cells. Biochem Biophys Res Commun. 2021;579:141-145. doi: 10.1016/j.bbrc.2021.09.024. DOI: https://doi.org/10.1016/j.bbrc.2021.09.024

Gioia U, Tavella S, Martinez-Orellana P, Cicio G, Colliva A, Ceccon M, et al. SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. Nat Cell Biol. 2023;25(4):550-564. doi: 10.1038/s41556-023-01096-x. DOI: https://doi.org/10.1038/s41556-023-01096-x

Ntouros PA, Vlachogiannis NI, Pappa M, Nezos A, Mavragani CP, Tektonidou MG, et al. Effective DNA damage response after acute but not chronic immune challenge: SARS-CoV-2 vaccine versus Systemic Lupus Erythematosus. Clin Immunol. 2021;229:108765. doi: 10.1016/j.clim.2021.108765. DOI: https://doi.org/10.1016/j.clim.2021.108765

Indraccolo S, Tisato V, Agata S, Moserle L, Ferrari S, Callegaro M, et al. Establishment and characterization of xenografts and cancer cell cultures derived from BRCA1 -/- epithelial ovarian cancers. Eur J Cancer. 2006;42(10):1475-1483. doi: 10.1016/j.ejca.2006.01.057. DOI: https://doi.org/10.1016/j.ejca.2006.01.057

Jiang H, Mei YF. SARS-CoV-2 spike impairs DNA damage repair and inhibits V(D)J recombination in vitro. Viruses. 2021;13(10):2056. doi: 10.3390/v13102056. DOI: https://doi.org/10.3390/v13102056

Egloff MP, Malet H, Putics A, Heinonen M, Dutartre H, Frangeul A, et al. Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. J Virol. 2006;80(17):8493-8502. doi: 10.1128/JVI.00713-06. DOI: https://doi.org/10.1128/JVI.00713-06

Fehr AR, Jankevicius G, Ahel I, Perlman S. Viral macrodomains: Unique mediators of viral replication and pathogenesis. Trends Microbiol. 2018;26(7):598-610. doi: 10.1016/j.tim.2017.11.011. DOI: https://doi.org/10.1016/j.tim.2017.11.011

Jankevicius G, Hassler M, Golia B, Rybin V, Zacharias M, Timinszky G, et al. A family of macrodomain proteins reverses cellular mono-ADP-ribosylation. Nat Struct Mol Biol. 2013;20(4):508-514. doi: 10.1038/nsmb.2523. DOI: https://doi.org/10.1038/nsmb.2523

Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913-917. doi: 10.1038/nature03443. DOI: https://doi.org/10.1038/nature03443

Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010;376(9737):245-251. doi: 10.1016/S0140-6736(10)60893-8. DOI: https://doi.org/10.1016/S0140-6736(10)60893-8

Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res. 2006;117(1):17-37. doi: 10.1016/j.virusres.2006.01.017. DOI: https://doi.org/10.1016/j.virusres.2006.01.017

Yan Q, Ding J, Khan SJ, Lawton LN, Shipp MA. DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites. iScience. 2023;26(4):106444. doi: 10.1016/j.isci.2023.106444. DOI: https://doi.org/10.1016/j.isci.2023.106444

Peng B, Shi R, Bian J, Li Y, Wang P, Wang H, et al. PARP1 and CHK1 coordinate PLK1 enzymatic activity during the DNA damage response to promote homologous recombination-mediated repair. Nucleic Acids Res. 2021;49(13):7554-7570. doi: 10.1093/nar/gkab584. DOI: https://doi.org/10.1093/nar/gkab584

Abuetabh Y, Wu HH, Chai C, Al Yousef H, Persad S, Sergi CM, et al. DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities. Exp Mol Med. 2022;54(10):1658-1669. doi: 10.1038/s12276-022-00863-4. DOI: https://doi.org/10.1038/s12276-022-00863-4

Li Q, Qian W, Zhang Y, Hu L, Chen S, Xia Y. A new wave of innovations within the DNA damage response. Signal Transduct Target Ther. 2023;8(1):338. doi: 10.1038/s41392-023-01548-8. DOI: https://doi.org/10.1038/s41392-023-01548-8

Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol. 2020;41(5):355-359. doi: 10.1016/j.it.2020.03.007. DOI: https://doi.org/10.1016/j.it.2020.03.007

Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020;9(1):382-385. doi: 10.1080/22221751.2020.1729069. DOI: https://doi.org/10.1080/22221751.2020.1729069

Coutant F, Touret F, Pin JJ, Alonzo M, Baronti C, Munier S, et al. Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants. Emerg Microbes Infect. 2024;13(1):2307510. doi: 10.1080/22221751.2024.2307510. DOI: https://doi.org/10.1080/22221751.2024.2307510

de Campos-Mata L, Trinite B, Modrego A, Tejedor Vaquero S, Pradenas E, Pons-Grifols A, et al. A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity. Nat Commun. 2024;15(1):1051. doi: 10.1038/s41467-024-45171-9. DOI: https://doi.org/10.1038/s41467-024-45171-9

Yang Y, Li F, Du L. Therapeutic nanobodies against SARS-CoV-2 and other pathogenic human coronaviruses. J Nanobiotechnol. 2024;22(1):304. doi: 10.1186/s12951-024-02573-7. DOI: https://doi.org/10.1186/s12951-024-02573-7

Additional Files

Published

2024-12-17

How to Cite

Chawsheen, M. A., Hassan , H. A., Al-Naqshbandi, A. A., Muhammad , H. A., Mahmood, M. H., Hamad Amin, A. H., … Hassan, Z. M. (2024). Effects of SARS-CoV-2 on DNA Damage Response Proteins Chk1 and P53: An in vitro Study. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 7(2), 151–156. https://doi.org/10.54133/ajms.v7i2.1513

Issue

Section

Original article

Similar Articles

1 2 3 4 > >> 

You may also start an advanced similarity search for this article.