Effects of aphidicolin on repair replication and induced chromosomal aberrations in mammalian cells

Zeeland, A.A. van; Bussmann, C.J.M.; Degrassi, Francesca; Filon, A.R.; Leeuwen, Anne C. van; Palitti, F.; Natarajan, A.T.

doi:10.1016/0027-5107(82)90237-8

Cited by 46 publications

(10 citation statements)

References 14 publications

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“…DNA repair replication was measured by the radioisotope and density labeling technique as described by Van Zeeland et al (30). 32 Porthophosphate prelabeled confluent human primary fibroblasts were X-irradiated (10 Gy or 30 Gy) in their culture medium (5 Gy/min).…”

Section: Measurement Of Dna Repair Replicationmentioning

confidence: 99%

“…Cells were lysed with 0.5% sodium lauroylsarcosinate, 0.01 M Tris and 0.01 M EDTA (pH 8) and incubated overnight with proteinase K (50 mg/ml) at 37uC. Cesium chloride density gradient centrifugation (two cycles of neutral and one alkaline centrifugation) and precipitation of DNA were performed as described previously (30). Repair replication was determined by liquid scintillation counting as the 3 H/ 32 P ratio in the parental DNA.…”

Section: Measurement Of Dna Repair Replicationmentioning

confidence: 99%

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Impaired Repair of Ionizing Radiation-Induced DNA Damage in Cockayne Syndrome Cells

et al. 2011

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Cockayne syndrome (CS) cells are defective in transcription-coupled repair (TCR) and sensitive to oxidizing agents, including ionizing radiation. We examined the hypothesis that TCR plays a role in ionizing radiation-induced oxidative DNA damage repair or alternatively that CS plays a role in transcription elongation after irradiation. Irradiation with doses up to 100 Gy did not inhibit RNA polymerase II-dependent transcription in normal and CS-B fibroblasts. In contrast, RNA polymerase I-dependent transcription was severely inhibited at 5 Gy in normal cells, indicating different mechanisms of transcription response to X rays. The frequency of radiation-induced base damage was 2 × 10(-7) lesions/base/Gy, implying that 150 Gy is required to induce one lesion/30-kb transcription unit; no TCR of X-ray-induced base damage in the p53 gene was observed. Therefore, it is highly unlikely that defective TCR underlies the sensitivity of CS to ionizing radiation. Overall genome repair levels of radiation-induced DNA damage measured by repair replication were significantly reduced in CS-A and CS-B cells. Taken together, the results do not provide evidence for a key role of TCR in repair of radiation-induced oxidative damages in human cells; rather, impaired repair of oxidative lesions throughout the genome may contribute to the CS phenotype.

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Section: Measurement Of Dna Repair Replicationmentioning

confidence: 99%

Section: Measurement Of Dna Repair Replicationmentioning

confidence: 99%

Impaired Repair of Ionizing Radiation-Induced DNA Damage in Cockayne Syndrome Cells

et al. 2011

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“…DNA repair replication in cells exposed to 10 J/m 2 UV-C was measured by the radioisotope and density labeling technique as previously described (17) with minor modifications.…”

Section: Methodsmentioning

confidence: 99%

Persistently stalled replication forks inhibit nucleotide excision repair in trans by sequestering Replication protein A

Tsaalbi-Shtylik

Moser

Mullenders

et al. 2014

Nucleic Acids Research

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Rev3, the catalytic subunit of DNA polymerase ζ, is essential for translesion synthesis of cytotoxic DNA photolesions, whereas the Rev1 protein plays a noncatalytic role in translesion synthesis. Here, we reveal that mammalian Rev3−/− and Rev1−/− cell lines additionally display a nucleotide excision repair (NER) defect, specifically during S phase. This defect is correlated with the normal recruitment but protracted persistence at DNA damage sites of factors involved in an early stage of NER, while repair synthesis is affected. Remarkably, the NER defect becomes apparent only at 2 h post-irradiation indicating that Rev3 affects repair synthesis only indirectly, rather than performing an enzymatic role in NER. We provide evidence that the NER defect is caused by scarceness of Replication protein A (Rpa) available to NER, resulting from its sequestration at stalled replication forks. Also the induction of replicative stress using hydroxyurea precludes the accumulation of Rpa at photolesion sites, both in Rev3−/− and in wild-type cells. These data support a model in which the limited Rpa pool coordinates replicative stress and NER, resulting in increased cytotoxicity of ultraviolet light when replicative stress exceeds a threshold.

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“…DNA repair replication in confluent normal human skin fibroblasts was measured by the radioisotope and density labeling technique described by van Zeeland et al. (11). In short, [ 32 P]‐orthophosphate prelabeled confluent cells were X‐irradiated (0.1, 1, 3 or 10 Gy) in their culture medium at several time intervals prior to UV irradiation.…”

mentioning

confidence: 99%

Enhanced Nucleotide Excision Repair in Human Fibroblasts Pre‐exposed to Ionizing Radiation

Cramers

Filon

Pines

et al. 2011

Photochem & Photobiology

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Cellular protection against deleterious effects of DNA damaging agents requires an intricate network of defense mechanisms known as the DNA damage response (DDR). Ionizing radiation (IR) mediated activation of the DDR induces a transcriptional upregulation of genes that are also involved in nucleotide excision repair (NER). This suggests that pre-exposure to X-rays might stimulate NER in human cells. Here, we demonstrate in normal human fibroblasts that UV-induced NER is augmented by pre-exposure to IR and that this increased repair is accompanied by elevated mRNA and protein levels of the NER factors XPC and DDB2. Furthermore, when IR exposure precedes local UV irradiation, the presence of XPC and DDB2 at the sites of local UV damages is increased. This increase might be p53 dependent, but the mechanism of X-ray specific stabilization of p53 is unclear as both X-rays and UV stabilize p53.

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Effects of aphidicolin on repair replication and induced chromosomal aberrations in mammalian cells

Cited by 46 publications

References 14 publications

Impaired Repair of Ionizing Radiation-Induced DNA Damage in Cockayne Syndrome Cells

Impaired Repair of Ionizing Radiation-Induced DNA Damage in Cockayne Syndrome Cells

Persistently stalled replication forks inhibit nucleotide excision repair in trans by sequestering Replication protein A

Enhanced Nucleotide Excision Repair in Human Fibroblasts Pre‐exposed to Ionizing Radiation

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