Dynamic recognition and repair of DNA complex damage

Yan, Junli; Xie, Youhua; Zhang, Qianjing; Gan, Lu; Wang, Fang; Li, Hongyan; Si, Jing; Zhang, Hong

doi:10.1002/jcp.27971

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…Earlier studies have shown that foci have a 1:1 association with DSBs, and the kinetics of foci disappearance reflect DSBs repair (Grudzenski et al, 2010). Herein, the maximal accumulation of foci in proliferating cells after a 1 h treatment period was followed by a gradual decrease, aligning with previous findings (Yan et al, 2019). However, delayed DNA damage and repair in quiescent cells were observed, which could be attributed to the lower killing effect of IR on HeLa cells in the quiescent state.…”

Section: Discussionsupporting

confidence: 92%

Carbon ions trigger DNA damage response to overcome radioresistance by regulating β‐catenin signaling in quiescent HeLa cells

Zhang

Xie

Liu

et al. 2023

Journal Cellular Physiology

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Quiescent cancer cells are major impediments to effective radiotherapy (RT) and exhibit limited sensitivity to traditional photon therapy. Herein, the functional role and underlying mechanism of carbon ions in overcoming the radioresistance of quiescent cervical cancer HeLa cells were determined. Briefly, serum withdrawal was used to induce synchronized quiescence in HeLa cells. Quiescent HeLa cells displayed strong radioresistance and DNA repair potential. After irradiation with carbon ions, the DNA damage repair pathway may markedly rely on error‐prone nonhomologous end‐joining in proliferating cells, whereas the high‐precision homologous recombination pathway is more relevant in quiescent cells. This phenomenon could be explained by the ionizing radiation (IR)‐induced cell cycle re‐entry of quiescent cancer cells. There are three strategies for eradicating quiescent cancer cells using high‐linear energy transfer (LET) carbon ions: direct cell death through complex DNA damage; apoptosis via an enhanced mitochondria‐mediated intrinsic pathway; forced re‐entry of quiescent cancer cells into the cell cycle, thereby improving their susceptibility to IR. Silencing β‐catenin signaling is essential for maintaining the dormant state in quiescent cells. Herein, carbon ions activated the β‐catenin pathway in quiescent cells, and inhibition of this pathway improved the resistance of quiescent HeLa cells to carbon ions by alleviating DNA damage, improving DNA damage repair, maintaining quiescent depth, and inhibiting apoptosis. Collectively, carbon ions conquer the radioresistance of quiescent HeLa cells by activating β‐catenin signaling, which provides a theoretical basis for improved therapeutic effects in patients with middle‐advanced‐stage cervical cancer with radioresistance.

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Section: Discussionsupporting

confidence: 92%

Carbon ions trigger DNA damage response to overcome radioresistance by regulating β‐catenin signaling in quiescent HeLa cells

Zhang

Xie

Liu

et al. 2023

Journal Cellular Physiology

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“…The principal biological effect of radiotherapy is to rapidly erase proliferating cells by inducing DNA damage beyond the cellular capacity to repair [18]. Once DNA was damaged, DNA repair proteins, such as Rad51, are recruited to DNA damage sites to form foci and repair damaged DNA [19]. We found that YAP overexpression cells displayed more numbers of Rad51 foci than vector cells after radiation, not only in U87 but also in GBM cells (Fig.…”

Section: Yap Promotes Dna Damage Repair Of Glioma Cells After Radiationmentioning

confidence: 71%

Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair

et al. 2021

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Although radiotherapy is a well-known effective non-surgical treatment for malignant gliomas, the therapeutic efficacy is severely limited due to the radioresistance of tumor cells. Previously, we demonstrated that Yes-associated protein (YAP) promotes glioma malignant progression. However, whether YAP plays a role in radioresistance and its potential value in cancer treatment are still unclear. In this study, we found that high YAP expression is associated with poor prognosis in malignant glioma patients undergoing radiotherapy. Research in immortalized cell lines and primary cells from GBM patients revealed that YAP exhibited a radioresistant effect on gliomas via promoting DNA damage repair. Mechanistically, after radiation, YAP was translocated into the nucleus, where it promoted the expression and secretion of FGF2, leading to MAPK–ERK pathway activation. FGF2 is a novel target gene of YAP. Inhibition of YAP–FGF2–MAPK signaling sensitizes gliomas to radiotherapy and prolongs the survival of intracranial cell-derived and patient-derived xenograft models. These results suggest that YAP–FGF2–MAPK is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy.

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“…Evidence has revealed that 12 C 6+ particles produce high levels of clustered DNA damage, including DSBs, which are implicated in cell lethality after irradiation (46,47). Since γ-H2AX has been demonstrated to form nuclear foci upon DSB, and previous studies have revealed that after irradiation with 12 C 6+ , a number of γ-H2AX foci increased at 4 h (48,49), in the present study, γ-H2AX expression was assessed 4 h post-irradiation, and further detected by immunofluorescence. The results indicated that after irradiation with 12 C 6+ , HeLa cells exhibited an increased number of γ-H2AX foci.…”

Section: Discussionmentioning

confidence: 99%

The effects of the Wnt/β‑catenin signaling pathway on apoptosis in HeLa cells induced by carbon ion irradiation

Zhang

Gan

et al. 2020

Oncol Rep

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The molecular mechanisms underlying the biological effects of carbon ions are unclear. The aim of this study was to explore the Wnt/β-catenin pathway in regulating carbon ion ( 12 C 6+ ) radiation-induced cellular toxicity. HLY78 is a Wnt-specific small molecular modulator, whose effects on 12 C 6+ radiation-induced damage are mostly unknown. HLY78, in combination with 12 C 6+ radiation was investigated on HeLa cell viability, cell cycle progression, DNA damage, and the expression of apoptotic and Wnt-related proteins. 12 C 6+ radiation suppressed cell viability in a time-dependent manner, whereas the addition of HLY78 to cells significantly reduced this stress. Moreover, after irradiation with 12 C 6+ , HeLa cells exhibited increased cell apoptosis, G2/M phase arrest, and a number of γ-H2AX foci. However, Wnt signaling activation alleviated these effects. Furthermore, when compared with the radiation alone group, supplementation with HLY78 markedly increased the expression of anti-apoptotic and Wnt-related proteins, and significantly decreased the expression of apoptotic proteins. The present results indicated that activation of the Wnt/β-catenin signaling pathway by HLY78 reduced 12 C 6+ radiation-induced HeLa cell dysfunction, suggesting that the Wnt/β-catenin signaling pathway plays an important role in regulating 12 C 6+ radiation-induced cellular toxicity in HeLa cells.

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Dynamic recognition and repair of DNA complex damage

Cited by 9 publications

References 37 publications

Carbon ions trigger DNA damage response to overcome radioresistance by regulating β‐catenin signaling in quiescent HeLa cells

Carbon ions trigger DNA damage response to overcome radioresistance by regulating β‐catenin signaling in quiescent HeLa cells

Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair

The effects of the Wnt/β‑catenin signaling pathway on apoptosis in HeLa cells induced by carbon ion irradiation

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