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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PAVLOPOULOU A., Asfa S., Gioukakis E., Mavragani I. V., Nikitaki Z., Takan I., ...Daha Fazla

MOLECULES, cilt.26, sa.24, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 24
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3390/molecules26247602
  • Dergi Adı: MOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: clustered DNA damage, ionizing radiation, cancer, comorbidities, prognosis, systems biology, IONIZING-RADIATION, REPAIR DISORDERS, BCL-2 FAMILY, DISEASE, RADIOSENSITIVITY, CONSEQUENCES, INDUCTION, RELEVANCE, ONTOLOGY, SURVIVAL
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

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.