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

45 Citations (Scopus)
177 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

Fingerprint

Repair
Radiation
DNA
Ionizing radiation
Ionizing Radiation
Cells
Molecules
Homologous Recombination
Radiotherapy
Eukaryotic Cells
Joining
Uncertainty
Ionization
Tumors
Pharmaceutical Preparations
Neoplasms
Proteins

Keywords

  • Radiation
  • DNA damage
  • DNA repair

Cite this

Kavanagh, Joy N. ; Redmond, Kelly M. ; Schettino, Giuseppe ; Prise, Kevin M. / DNA double strand break repair: a radiation perspective. In: Antioxidants & Redox Signaling. 2013 ; Vol. 18, No. 18. pp. 2458-2472.
@article{434de7a32bed49f18b31f88766530824,
title = "DNA double strand break repair: a radiation perspective",
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.",
keywords = "Radiation, DNA damage, DNA repair",
author = "Kavanagh, {Joy N.} and Redmond, {Kelly M.} and Giuseppe Schettino and Prise, {Kevin M.}",
year = "2013",
month = "6",
day = "3",
doi = "10.1089/ars.2012.5151",
language = "English",
volume = "18",
pages = "2458--2472",
journal = "Antioxidants & Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "18",

}

DNA double strand break repair: a radiation perspective. / Kavanagh, Joy N.; Redmond, Kelly M.; Schettino, Giuseppe; Prise, Kevin M.

In: Antioxidants & Redox Signaling, Vol. 18, No. 18, 03.06.2013, p. 2458-2472.

Research output: Contribution to journalLiterature review

TY - JOUR

T1 - DNA double strand break repair: a radiation perspective

AU - Kavanagh, Joy N.

AU - Redmond, Kelly M.

AU - Schettino, Giuseppe

AU - Prise, Kevin M.

PY - 2013/6/3

Y1 - 2013/6/3

N2 - 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.

AB - 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.

KW - Radiation

KW - DNA damage

KW - DNA repair

U2 - 10.1089/ars.2012.5151

DO - 10.1089/ars.2012.5151

M3 - Literature review

VL - 18

SP - 2458

EP - 2472

JO - Antioxidants & Redox Signaling

JF - Antioxidants & Redox Signaling

SN - 1523-0864

IS - 18

ER -