In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach

Pavlopoulou, Athanasia; Asfa, Seyedehsadaf; Gioukakis, Evangelos; Mavragani, Ifigeneia V.; Nikitaki, Zacharenia; Takan, Işıl; Pouget, Jean-Pierre; Harrison, Lynn; Georgakilas, Alexandros G.

doi:10.3390/molecules26247602

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In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach

Athanasia Pavlopoulou

^1,2,†

Seyedehsadaf Asfa

^1,2,†

Evangelos Gioukakis

Ifigeneia V. Mavragani

³,

^1,2

⁴,

⁵ and

Alexandros G. Georgakilas

^3,*

Izmir Biomedicine and Genome Center, Balcova, Izmir 35340, Turkey

Izmir International Biomedicine and Genome Institute, Genomics and Molecular Biotechnology Department, Dokuz Eylül University, Balcova, Izmir 35220, Turkey

Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 15780 Zografou, Greece

⁴

IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, 34298 Montpellier, France

⁵

Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editors: Boleslaw Karwowski and Jussara Amato

Molecules 2021, 26(24), 7602; https://doi.org/10.3390/molecules26247602

Received: 4 November 2021 / Revised: 7 December 2021 / Accepted: 11 December 2021 / Published: 15 December 2021

(This article belongs to the Special Issue The Beauty of Clustered DNA Lesion)

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Abstract

Different types of DNA lesions forming in close vicinity, create clusters of damaged sites termed as “clustered/complex DNA damage” and they are considered to be a major challenge for DNA repair mechanisms resulting in significant repair delays and induction of genomic instability. Upon detection of DNA damage, the corresponding DNA damage response and repair (DDR/R) mechanisms are activated. The inability of cells to process clustered DNA lesions efficiently has a great impact on the normal function and survival of cells. If complex lesions are left unrepaired or misrepaired, they can lead to mutations and if persistent, they may lead to apoptotic cell death. In this in silico study, and through rigorous data mining, we have identified human genes that are activated upon complex DNA damage induction like in the case of ionizing radiation (IR) and beyond the standard DNA repair pathways, and are also involved in cancer pathways, by employing stringent bioinformatics and systems biology methodologies. Given that IR can cause repair resistant lesions within a short DNA segment (a few nm), thereby augmenting the hazardous and toxic effects of radiation, we also investigated the possible implication of the most biologically important of those genes in comorbid non-neoplastic diseases through network integration, as well as their potential for predicting survival in cancer patients. View Full-Text

Keywords: clustered DNA damage; ionizing radiation; cancer; comorbidities; prognosis; systems biology

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Pavlopoulou, A.; Asfa, S.; Gioukakis, E.; Mavragani, I.V.; Nikitaki, Z.; Takan, I.; Pouget, J.-P.; Harrison, L.; Georgakilas, A.G. In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach. Molecules 2021, 26, 7602. https://doi.org/10.3390/molecules26247602

AMA Style

Pavlopoulou A, Asfa S, Gioukakis E, Mavragani IV, Nikitaki Z, Takan I, Pouget J-P, Harrison L, Georgakilas AG. In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach. Molecules. 2021; 26(24):7602. https://doi.org/10.3390/molecules26247602

Chicago/Turabian Style

Pavlopoulou, Athanasia, Seyedehsadaf Asfa, Evangelos Gioukakis, Ifigeneia V. Mavragani, Zacharenia Nikitaki, Işıl Takan, Jean-Pierre Pouget, Lynn Harrison, and Alexandros G. Georgakilas. 2021. "In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach" Molecules 26, no. 24: 7602. https://doi.org/10.3390/molecules26247602

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In Silico Investigation of the Biological Implications of Complex DNA Damage with Emphasis in Cancer Radiotherapy through a Systems Biology Approach

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