The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks

Zhao, Lei; Bao, Chengyu; Shang, Yuxuan; He, Xinye; Ma, Chiyuan; Lei, Xiaohua; Mi, Dong; Sun, Yeqing

doi:10.1155/2020/4834965

Cited by 38 publications

(37 citation statements)

References 87 publications

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“…Fast processes involve repair by DSB end resection-independent NHEJ, and in slow repair, such as DSB repair in heterochromatin regions or cluster DNA damage, BRCA1 activity results in DSB end resection [ 19 , 38 , 39 ]. In the S/G2 phase, DSB end resection continues to HR, whereas DSB repair occurs through the slow process of DSB end resection-dependent NHEJ in the G1 phase [ 36 , 40 , 41 , 42 ]. Microscopically, 53BP1 repositioning for DSB end resection associated with BRCA1 activation is reported to result in a larger focal size at 2 h post-irradiation than immediately after irradiation using ionizing radiation [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation

Oizumi

Ohno

Yamabe

et al. 2020

Life

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Radiation is unavoidable in space. Energetic particles in space radiation are reported to induce cluster DNA damage that is difficult to repair. In this study, normal human fibroblasts were irradiated with components of space radiation such as proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure.

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Section: Discussionmentioning

confidence: 99%

Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation

Oizumi

Ohno

Yamabe

et al. 2020

Life

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“…Moreover, chromatin is hierarchically organized at multiple scale levels, which leads to the formation of structurally and functionally distinct chromatin domains [44][45][46][47], with which radiation interacts in a specific way and creates DNA lesions with different requirements for repair (reviewed in [48][49][50][51][52]). The chemical properties of the broken DNA ends were the first local factor ( Figure 1D) recognized to dramatically affect the ability of repair enzymes to rejoin DSBs [53].…”

Section: Global Versus Local Dsb Repair Pathway Selection and Regulationmentioning

confidence: 99%

“…IRIF formation and disassembly have been studied in great detail for opened, genetically active euchromatin and condensed, genetically inactive heterochromatin ( Figure 3) (reviewed in [48,[50][51][52][83][84][85][86][87]). In our previous study [76], we used IRIF microscopy to compare radiation damage and repair also for regions of increased gene expression (RIDGEs) [88,89] and anti-RIDGEs, representing domains even more structurally and functionally distinct than euchromatin and heterochromatin.…”

Section: Is Regulation Of Dsb Repair Physically Controlled Through Chmentioning

confidence: 99%

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

Falk

Hausmann

2020

Cancers

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DNA double-strand breaks (DSBs) have been recognized as the most serious lesions in irradiated cells. While several biochemical pathways capable of repairing these lesions have been identified, the mechanisms by which cells select a specific pathway for activation at a given DSB site remain poorly understood. Our knowledge of DSB induction and repair has increased dramatically since the discovery of ionizing radiation-induced foci (IRIFs), initiating the possibility of spatiotemporally monitoring the assembly and disassembly of repair complexes in single cells. IRIF exploration revealed that all post-irradiation processes—DSB formation, repair and misrepair—are strongly dependent on the characteristics of DSB damage and the microarchitecture of the whole affected chromatin domain in addition to the cell status. The microscale features of IRIFs, such as their morphology, mobility, spatiotemporal distribution, and persistence kinetics, have been linked to repair mechanisms. However, the influence of various biochemical and structural factors and their specific combinations on IRIF architecture remains unknown, as does the hierarchy of these factors in the decision-making process for a particular repair mechanism at each individual DSB site. New insights into the relationship between the physical properties of the incident radiation, chromatin architecture, IRIF architecture, and DSB repair mechanisms and repair efficiency are expected from recent developments in optical superresolution microscopy (nanoscopy) techniques that have shifted our ability to analyze chromatin and IRIF architectures towards the nanoscale. In the present review, we discuss this relationship, attempt to correlate still rather isolated nanoscale studies with already better-understood aspects of DSB repair at the microscale, and consider whether newly emerging “correlated multiscale structuromics” can revolutionarily enhance our knowledge in this field.

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“…From this perspective, the impact of ultrashort pulsed irradiation on DNA and particularly on one of the most deleterious lesions, namely double strand breaks (DSBs) formation on both qualitative and quantitative levels is of high interest. It is widely accepted that DSBs are the main trigger for the initiation of cellular processes in response to ionizing radiation [ 8 , 9 ]. About 80% of irradiation-induced DSBs are repaired by a relatively fast (up to 4–6 h), but error-prone mechanism of nonhomologous end joining, which often results in microdeletions and chromosomal aberrations [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Low Repair Capacity of DNA Double-Strand Breaks Induced by Laser-Driven Ultrashort Electron Beams in Cancer Cells

Babayan

Vorobyeva

Grigoryan

et al. 2020

IJMS

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Laser-driven accelerators allow to generate ultrashort (from femto- to picoseconds) high peak dose-rate (up to tens of GGy/s) accelerated particle beams. However, the radiobiological effects of ultrashort pulsed irradiation are still poorly studied. The aim of this work was to compare the formation and elimination of γH2AX and 53BP1 foci (well known markers for DNA double-strand breaks (DSBs)) in Hela cells exposed to ultrashort pulsed electron beams generated by Advanced Research Electron Accelerator Laboratory (AREAL) accelerator (electron energy 3.6 MeV, pulse duration 450 fs, pulse repetition rates 2 or 20 Hz) and quasi-continuous radiation generated by Varian accelerator (electron energy 4 MeV) at doses of 250–1000 mGy. Additionally, a study on the dose–response relationships of changes in the number of residual γH2AX foci in HeLa and A549 cells 24 h after irradiation at doses of 500–10,000 mGy were performed. We found no statistically significant differences in γH2AX and 53BP1 foci yields at 1 h after exposure to 2 Hz ultrashort pulse vs. quasi-continuous radiations. In contrast, 20 Hz ultrashort pulse irradiation resulted in 1.27-fold higher foci yields as compared to the quasi-continuous one. After 24 h of pulse irradiation at doses of 500–10,000 mGy the number of residual γH2AX foci in Hela and A549 cells was 1.7–2.9 times higher compared to that of quasi-continuous irradiation. Overall, the obtained results suggest the slower repair rate for DSBs induced by ultrashort pulse irradiation in comparison to DSBs induced by quasi-continuous irradiation.

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The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks

Cited by 38 publications

References 87 publications

Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation

Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

Low Repair Capacity of DNA Double-Strand Breaks Induced by Laser-Driven Ultrashort Electron Beams in Cancer Cells

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