Repair of DNA Double-Strand Breaks in Irradiated Yeast Cells under Nongrowth Conditions

Frankenberg-Schwager, M.; Frankenberg, D.; Blöcher, D.; Adamczyk, C.; Blocher, D.

doi:10.2307/3575316

Cited by 65 publications

(14 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This would provide the opportunity to treat d/N 0 as a parameter proportional to RBE for cell kill and to measure RBE in terms of the repair kinetics of the cellular DNA. Assuming DSB is the dominant type of unrepairable damage and that this unrepairable damage is the main cause of cell death [10,32,33], several authors have reported a quadratic relationship between dose and the unrepaired fraction of DSB after different repair periods [30,34,35], hence the relationship between d/N 0 and RBE for cell inactivation could be formulated as:…”

Section: Discussionmentioning

confidence: 99%

Repair kinetic considerations in particle beam radiotherapy

Carabe‐Fernandez

Dale²,

Paganetti³

2011

BJR

View full text Add to dashboard Cite

Objectives: A second-order repair kinetics model is developed to predict damage repair rates following low or high linear energy transfer (LET) irradiations and to assess the amount of unrepairable damage produced by such radiations. The model is a further development of an earlier version designed to test if low-LET radiation repair processes could be quantified in terms of second-order kinetics. The newer version allows calculation of both the repair rate of the proportion of DNA damages that repair according to secondorder kinetics and the proportion of DNA damages that do not repair. Methods: The original and present models are intercompared in terms of their goodness-of-fit to a number of data sets obtained from different ion beams. The analysis demonstrates that the present model provides a better fit to the data in all cases studied. Results: The proportions of unrepairable damage created by radiations of different LET predicted by the new model correspond well with previous studies on the increased effectiveness of high-LET radiations in inducing reproductive cell death. The results show that the original model may underestimate the proportion of unrepaired damage at any given time after its creation as well as failing to predict very slow or unrepairable damage components, which may result from high-LET irradiation. Conclusion: It is suggested that the second-order model presented here offers a more realistic view of the patterns of repair in cell lines or tissues exposed to high-LET radiation. investigations provide evidence that radiations of different linear energy transfer (LET) produce different types of DNA damage and that a larger proportion of complex damage is being created by higher LET. There is also evidence that different types of DNA damage are associated with different repair rates, with more complex damage taking longer to repair (if at all) [3,4]. It has been reported [5,6] that highly complex DNA breaks imply in some cases such a massive loss of DNA coding that the chances of correct repair are very low.For a given particle type, the relative biological effectiveness (RBE) increases with LET until reaching a maximum and then decreases. Belli et al [7] have recently studied the repair characteristics of double-strand breaks (DSBs) produced by radiations of different LET, arriving at the conclusion that the increase in RBE for cell inactivation with LET might be related to the increasing proportion of unrepaired DSB rather than the proportion of induced DSB. A similar conclusion was reached by Barendsen [1,8,9], who studied the LET dependency of different types of DNA strand breaks and suggested different candidates of DNA damage to explain cell inactivation. Other authors also have found a correspondence between unrepaired DNA strand breaks and cell lethality (e.g. Ritter et al [10], Goodhead et al [11] and more recently Eguchi-Kasai et al [12]), but none of them provided information on the specific nature of the unrepairable DNA strand breaks.In practical terms, DNA DSBs with very slow...

show abstract

Section: Discussionmentioning

confidence: 99%

Repair kinetic considerations in particle beam radiotherapy

Carabe‐Fernandez

Dale²,

Paganetti³

2011

BJR

View full text Add to dashboard Cite

show abstract

“…Furthermore, the repair of DSB during liquid holding has been shown indicating that unrepaired DSB constitute the PLD [7]. From the LHR data presented here it could be suggested that the rad50 to 57 loci (rad52 group) could be involved in the repair of DSB and that while the repair of DSB is partially impaired in the rad53, 55, and 57 strains, it is totally absent in the rad50, 51, 52, and 54 strains.…”

Section: Lhr Studies In Radiosensitive Yeast Strainsmentioning

confidence: 70%

Genetic control of repair of radiation damage produced under euoxic and anoxic conditions in diploid yeastSaccharomyces cerevisiae

Reddy

Rao

1981

Radiat Environ Biophys

View full text Add to dashboard Cite

Summary. Diploid wild type yeast strains 211, X2180 and the radiation sensitive mutants rad2, 6, 9, 18, 50-55, and 57 were exposed to cobalt-60 gamma radiation, in the presence and absence of oxygen, in order to identify the RAD loci involved in the repair of sublethal damage (SLD), recovery from potentially lethal damage (PLD) and oxygen enhancement ratio (OER). Response of wild type and mutants were compared in terms of survival curve parameters Dq, D10, D1, and Do. As compared to wild type the mutants showed increased sensitivity to radiation lethality, both under euoxic and hypoxic conditions, as judged by the reduction in Dq and Do values. OER was reduced in the rad2, 9, 18, 50, 51, and 57 mutants indicating that these genes could be associated with the repair of gamma radiation damage produced under hypoxic condition.Shoulder (Dq) a measure of the ability of the cells to repair SLD, was reduced in the rad6, 9, 18, 50, 53, and 57 strains and was almost absent in the rad51, 52, 54, and 55 mutants. The ability to recover from PLD was equal to that of wild type strain in the rad2, 6, 9, and 18 strains, reduced in the rad53, 55, and 57 strains and was absent in the rad50-52 and 54 strains. In the mutants with liquid holding recovery ability, the extent of recovery from PLD produced under euoxic and hypoxic conditions was the same. These observations suggest that different groups of loci are involved in the control of different repair processes and that the expression of the rad50-57 loci play a very important role in the repair of ionising radiation damage. On the basis of the liquid holding recovery data presented here and the observations made by others it is suggested that the unrepaired DSB constitute the PLD and that the repair of DSB involves recombination between homologous chromosomes.

show abstract

“…This finding indicates that HCC cells, upon exposure to radiation, markedly and differently activate or deactivate genes between early and late phases after irradiation. When radiation-responsive genes were classified according to their function using gene ontology, we found that DNA repairassociated genes were well matched with radiation sensitivity among other classes of physiologically relevant genes, and the inability to repair double-strand breaks induced by radiation may cause cell death (20,21). In the present study, relatively radiation-resistant HepG2 cells showed up-regulation of a substantial fraction of DNA repair-associated genes, including Ku70, PMS1, MSH6, DNA-dependent protein kinase, and ERCC5 genes.…”

Section: Discussionmentioning

confidence: 97%

Temporal cDNA microarray analysis of gene expression in human hepatocellular carcinoma upon radiation exposure

Jeong

Hong²,

Ju³

et al. 2006

Oncol Rep

View full text Add to dashboard Cite

Radiotherapy is not commonly used for the treatment of human hepatocellular carcinoma, due to its poor response rate and poor tolerance of normal liver to ionizing radiation. Recently developed microarray technology makes it possible to verify genes responsive to anticancer therapy of human cancers by simultaneous analysis of gene expression profiles. In the present study, the expression profile of radiationresponsive genes in human hepatocellular carcinoma was evaluated through time-dependent cDNA microarray analysis of expressional variation, following exposure to ionizing radiation. Upon exposure to radiation, more than 13% of genes in both radiation-resistant and-sensitive cells responded to radiation. Time-dependent analysis of radiation-responsive genes revealed that, irrespective of radiation sensitivity, greatly different subsets of genes sequentially participated in cellular response to radiation at their specific activation or deactivation time points. The majority of radiation-responsive genes were differentially but not commonly expressed between radiationresistant and-sensitive cells. When these differentially regulated genes were classified according to their physiological and functional characteristics and radiation sensitivity, it was prominently obvious that DNA repair-promoting genes were up-regulated in radio-resistant cells and down-regulated or unchanged in radiation-sensitive cells. The present findings indicate that different subsets of genes are sequentially working and DNA repair capacity may control the radiation sensitivity of human hepatocellular carcinoma cells more than any other physiological factor.

show abstract

Repair of DNA Double-Strand Breaks in Irradiated Yeast Cells under Nongrowth Conditions

Cited by 65 publications

References 0 publications

Repair kinetic considerations in particle beam radiotherapy

Repair kinetic considerations in particle beam radiotherapy

Genetic control of repair of radiation damage produced under euoxic and anoxic conditions in diploid yeastSaccharomyces cerevisiae

Temporal cDNA microarray analysis of gene expression in human hepatocellular carcinoma upon radiation exposure

Contact Info

Product

Resources

About