DNA Double Strand Break Repair Pathways in Response to Different Types of Ionizing Radiation

Kamp, Gerarda van de; Heemskerk, Tim; Kanaar, Roland; Essers, Jeroen

doi:10.3389/fgene.2021.738230

Cited by 21 publications

(12 citation statements)

References 127 publications

(221 reference statements)

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“…These and other aberrant DNA structures trigger a multifaceted network of DNA damage response signaling and lead to the subsequent removal of DNA lesions by various dedicated and complementary DNA repair processes [18,157]. These include amongst others homologous recombination (HR) and non-homologous end joining (NHEJ) for the repair of double-stranded DNA breaks [158], base excision repair (BER) for the removal of subtle base modifications [159], global genome-nucleotide excision repair (GG-NER) and transcription-coupled repair (TCR) for bulky helix distorting lesions [160], and interstrand crosslink (ICL) repair to resolve DNA crosslinks during replication [161] (Figure 2). Translesion synthesis polymerases can still bypass damaged DNA bases during replication giving rise to increased mutations over time [162].…”

Section: Conceptualization Of Chemotherapeutics Driving Segmental Agingmentioning

confidence: 99%

Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Boogaard

Komninos

Vermeij

2022

Cancers

153

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Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible.

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Section: Conceptualization Of Chemotherapeutics Driving Segmental Agingmentioning

confidence: 99%

Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Boogaard

Komninos

Vermeij

2022

Cancers

153

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“…The full complexities of these pathways have been extensively reviewed elsewhere [ 5 , 6 ]. DSBs arise from both endogenous and exogenous sources, such as free radicals and ionizing radiation, respectively [ 7 , 8 ], as well as V(D)J recombination and class switch recombination (CSR) [ 9 , 10 ]. SSBs can be induced by ionizing radiation, reactive oxygen species (ROS), and as a result of replication errors resulting in single strand DNA (ssDNA) [ 11 , 12 ].…”

Section: The Dna Damage Responsementioning

confidence: 99%

Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response

López

Bouchier‐Hayes

2022

Cells

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Members of the caspase family are well known for their roles in the initiation and execution of cell death. Due to their function in the removal of damaged cells that could otherwise become malignant, caspases are important players in the DNA damage response (DDR), a network of pathways that prevent genomic instability. However, emerging evidence of caspases positively or negatively impacting the accumulation of DNA damage in the absence of cell death demonstrates that caspases play a role in the DDR that is independent of their role in apoptosis. This review highlights the apoptotic and non-apoptotic roles of caspases in the DDR and how they can impact genomic stability and cancer treatment.

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“…Therefore, a large fraction of DSB induced by charged particles is still processed by c-NHEJ, similarly to X-rays. Some data show that mammalian cells resort more often to HR than NHEJ to process clustered DNA lesions ( Refs 46,47,48). Surprisingly, measuring DSB repair kinetics in repair-deficient cell lines, some authors found that after proton therapy (low-LET, similar to X-rays), there was an almost complete shift from NHEJ to HR (Refs 49, 50, 51).…”

Section: Dna Repair Pathwaysmentioning

confidence: 99%

Particle radiotherapy and molecular therapies: mechanisms and strategies towards clinical applications

Helm

Fournier

Durante

2022

Expert Rev. Mol. Med.

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Immunotherapy and targeted therapy are now commonly used in clinical trials in combination with radiotherapy for several cancers. While results are promising and encouraging, the molecular mechanisms of the interaction between the drugs and radiation remain largely unknown. This is especially important when switching from conventional photon therapy to particle therapy using protons or heavier ions. Different dose deposition patterns and molecular radiobiology can in fact modify the interaction with drugs and their effectiveness. We will show here that whilst the main molecular players are the same after low and high linear energy transfer radiation exposure, significant differences are observed in post-exposure signalling pathways that may lead to different effects of the drugs. We will also emphasise that the problem of the timing between drug administration and radiation and the fractionation regime are critical issues that need to be addressed urgently to achieve optimal results in combined treatments with particle therapy.

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DNA Double Strand Break Repair Pathways in Response to Different Types of Ionizing Radiation

Cited by 21 publications

References 127 publications

Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response

Particle radiotherapy and molecular therapies: mechanisms and strategies towards clinical applications

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