DNA double strand break repair: a radiation perspective

Joy N. Kavanagh, Kelly M. Redmond, Giuseppe Schettino, Kevin M. Prise

Research output: Contribution to journalLiterature review

47 Citations (Scopus)
282 Downloads (Pure)

Abstract

SIGNIFICANCE:
Ionizing radiation (IR) can induce a wide range of unique deoxyribonucleic acid (DNA) lesions due to the spatiotemporal correlation of the ionization produced. Of these, DNA double strand breaks (DSBs) play a key role. Complex mechanisms and sophisticated pathways are available within cells to restore the integrity and sequence of the damaged DNA molecules.
RECENT ADVANCES:
Here we review the main aspects of the DNA DSB repair mechanisms with emphasis on the molecular pathways, radiation-induced lesions, and their significance for cellular processes.
CRITICAL ISSUES:
Although the main characteristics and proteins involved in the two DNA DSB repair processes present in eukaryotic cells (homologous recombination and nonhomologous end-joining) are reasonably well established, there are still uncertainties regarding the primary sensing event and their dependency on the complexity, location, and time of the damage. Interactions and overlaps between the different pathways play a critical role in defining the repair efficiency and determining the cellular functional behavior due to unrepaired/miss-repaired DNA lesions. The repair pathways involved in repairing lesions induced by soluble factors released from directly irradiated cells may also differ from the established response mechanisms.
FUTURE DIRECTIONS:
An improved understanding of the molecular pathways involved in sensing and repairing damaged DNA molecules and the role of DSBs is crucial for the development of novel classes of drugs to treat human diseases and to exploit characteristics of IR and alterations in tumor cells for successful radiotherapy applications.
Original languageEnglish
Pages (from-to)2458-2472
Number of pages15
JournalAntioxidants & Redox Signaling
Volume18
Issue number18
Early online date21 Mar 2013
DOIs
Publication statusPublished - 03 Jun 2013

Keywords

  • Radiation
  • DNA damage
  • DNA repair

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

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