GTPases, genome, actin: A hidden story in DNA damage response and repair mechanisms

Magalhães, Yuli Thamires; Farias, Jéssica Oliveira; Silva, Luiz Eduardo da; Forti, Fábio Luís

doi:10.1016/j.dnarep.2021.103070

Cited by 24 publications

(15 citation statements)

References 192 publications

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“…Rho/ROCK has also been proven to regulate DNA damage responses and repair mechanisms [ 61 ]. In melanoma, ROCK inhibitor treatment induced reactive oxygen species (ROS) generation by lowering the contractility of cancer cells, leading to DNA damage responses in vitro [ 62 ]. ROCK2 was also shown to be involved in centrosome complex formation with BRCA2 in breast cancer, indicating the possibility that ROCK2 inhibition may induce DNA damage [ 63 ].…”

Section: Targeting Rock For Cancer Treatmentmentioning

confidence: 99%

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Kim

Han

et al. 2021

IJMS

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Cancer immunotherapy is fast rising as a prominent new pillar of cancer treatment, harnessing the immune system to fight against numerous types of cancer. Rho-kinase (ROCK) pathway is involved in diverse cellular activities, and is therefore the target of interest in various diseases at the cellular level including cancer. Indeed, ROCK is well-known for its involvement in the tumor cell and tumor microenvironment, especially in its ability to enhance tumor cell progression, migration, metastasis, and extracellular matrix remodeling. Importantly, ROCK is also considered to be a novel and effective modulator of immune cells, although further studies are needed. In this review article, we describe the various activities of ROCK and its potential to be utilized in cancer treatment, particularly in cancer immunotherapy, by shining a light on its activities in the immune system.

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Section: Targeting Rock For Cancer Treatmentmentioning

confidence: 99%

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Kim

Han

et al. 2021

IJMS

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“…Furthermore, both cascades are involved in apoptosis induction as a consequence of DNA damage. Here, DNA damage-associated γ H2A.X regulates Rac1/NOX1-mediated increase in intracellular ROS concentration [ 86 ]. A growing body of evidence supports the assumption that γ H2A.X occurrence in correlation or noncorrelation with DNA lesions is far more complex.…”

Section: Histone γ H2axmentioning

confidence: 99%

H2A.X Phosphorylation in Oxidative Stress and Risk Assessment in Plasma Medicine

Schütz

Stope²,

Bekeschus

2021

Oxidative Medicine and Cellular Longevity

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At serine139-phosphorylated gamma histone H2A.X (γH2A.X) has been established over the decades as sensitive evidence of radiation-induced DNA damage, especially DNA double-strand breaks (DSBs) in radiation biology. Therefore, γH2A.X has been considered a suitable marker for biomedical applications and a general indicator of direct DNA damage with other therapeutic agents, such as cold physical plasma. Medical plasma technology generates a partially ionized gas releasing a plethora of reactive oxygen and nitrogen species (ROS) simultaneously that have been used for therapeutic purposes such as wound healing and cancer treatment. The quantification of γH2A.X as a surrogate parameter of direct DNA damage has often been used to assess genotoxicity in plasma-treated cells, whereas no sustainable mutagenic potential of the medical plasma treatment could be identified despite H2A.X phosphorylation. However, phosphorylated H2A.X occurs during apoptosis, which is associated with exposure to cold plasma and ROS. This review summarizes the current understanding of γH2A.X induction and function in oxidative stress in general and plasma medicine in particular. Due to the progress towards understanding the mechanisms of H2A.X phosphorylation in the absence of DSB and ROS, observations of γH2A.X in medical fields should be carefully interpreted.

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“…As relevant key regulators of cytoskeletal dynamics and intracellular signaling, Rho family guanosine triphosphatases (GTPases) are crucial for the regulation of several fundamental biological processes in various cell types, including cell cycle progression, gene transcription, and cell morphology, motility, and polarity [ 3 ]. Furthermore, the direct modulation of Rho GTPase activity has emerged as a relevant contributor to the maintenance of genomic stability, which is implicated in a variety of human conditions [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What’s behind Neuro-RACopathies

Scala

Nishikawa

Nagata

et al. 2021

Cells

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Rho family guanosine triphosphatases (GTPases) regulate cellular signaling and cytoskeletal dynamics, playing a pivotal role in cell adhesion, migration, and cell cycle progression. The Rac subfamily of Rho GTPases consists of three highly homologous proteins, Rac 1–3. The proper function of Rac1 and Rac3, and their correct interaction with guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs) are crucial for neural development. Pathogenic variants affecting these delicate biological processes are implicated in different medical conditions in humans, primarily neurodevelopmental disorders (NDDs). In addition to a direct deleterious effect produced by genetic variants in the RAC genes, a dysregulated GTPase activity resulting from an abnormal function of GEFs and GAPs has been involved in the pathogenesis of distinctive emerging conditions. In this study, we reviewed the current pertinent literature on Rac-related disorders with a primary neurological involvement, providing an overview of the current knowledge on the pathophysiological mechanisms involved in the neuro-RACopathies.

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GTPases, genome, actin: A hidden story in DNA damage response and repair mechanisms

Cited by 24 publications

References 192 publications

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential

H2A.X Phosphorylation in Oxidative Stress and Risk Assessment in Plasma Medicine

Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What’s behind Neuro-RACopathies

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