Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.15810

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Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.15623

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Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.15260

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Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bbrc.2015.10.125

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Publishing type：Research paper (scientific journal)  

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Publishing type：Research paper (scientific journal)  

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Publishing type：Research paper (scientific journal)  

DOI： 10.1155/2014/193816

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Publishing type：Research paper (scientific journal)  

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Publishing type：Research paper (scientific journal)  

Werner syndrome (WS), caused by mutations in a gene (WRN) that encodes a RecQ DNA helicase, is characterized by premature aging and cancer predisposition. Cells derived from WS patients show sensitivity to several DNA damaging agents. Previous studies revealed that the WRN protein plays roles in DNA repair or damage tolerance, although it was not yet assigned to a specific pathway. Here we examined the relationship between WRN and the post-replication repair protein RAD18 by generating deletion derivatives in chicken DT40 cells. The frequency of spontaneous sister chromatid exchange in WRN(-/-)/RAD18(-/-) double mutant cells was slightly increased compared to that of either single mutant. However, the sensitivity of WRN(-/-)/RAD18(-/-) cells to 4-nitroquinoline 1-oxide and methyl methanesulfonate was almost the same as that of RAD18(-/-) cells. Moreover, the cisplatin sensitivity of RAD18(-/-) cells was slightly suppressed by disruption of WRN. These data suggest that WRN functions in a pathway involving RAD18 under damage-inducing conditions.

DOI： 10.1248/bpb.30.1080

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Publishing type：Research paper (scientific journal)  

We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70(-/-)/WRN(-/-) and DNA-PKcs(-/-/-)/WRN(-/-) double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN(-/-) cells showed higher sensitivity than wild-type cells, whereas KU70(-/-) and DNA-PKcs(-/-/-) cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN(-/-) cells to CPT, rendering them as resistant to CPT treatment as KU70(-/-) and DNA-PKcs(-/-/-) cells. On the other hand, CPT sensitivity of BLM(-/-) cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.

DOI： 10.1016/j.bbrc.2007.01.175

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Publishing type：Research paper (scientific journal)  

Mutations in RecQL4 are a causative factor in Rothmund-Thomson syndrome, a human autosomal recessive disorder characterized by premature aging. To study the role of RecQL4, we employed a cell-free experimental system consisting of Xenopus egg extracts. RecQL4 loading onto chromatin was observed regardless of the presence or absence of EcoRI. However, in the absence of EcoRI, RecQL4 loading was suppressed by geminin, an inhibitor of pre-replicative complex formation, while in the presence of EcoRI, it was not affected. These results suggest that under the former condition, RecQL4-loading depended on DNA replication, while under the latter, the interaction occurred in response to double-stranded DNA breaks (DSBs) induced by EcoRI. DSB-induced RecQL4 loading depended on the function of the ataxia-telangiectasia mutated protein, DNA-dependent protein kinase (DNA-PK), and replication protein A, while there were only minor changes in DNA replication-associated RecQL4 loading upon suppression of these proteins. Furthermore, analyses using a chromatin-immunoprecipitation assay and quantification of gammaH2AX after induction of DSBs suggested that RecQL4 is loaded adjacent to Ku heterodimer-binding sites on damaged chromatin, and functions in the repair of DSBs.

DOI： 10.1016/j.bbamcr.2007.01.005

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Language：English  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：English  

DOI： 10.1371/journal.pone.0110577

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Publisher：Hindawi Limited  

<italic>Introduction</italic>. Prenatal programming secondary to maternal protein restriction renders an inherent susceptibility to neural compromise in neonates and any addition of glucocorticosteroids results in further damage. This is an investigation of consequent global gene activity due to effects of antenatal steroid therapy on a protein restriction mouse model. <italic>Methods</italic>. C57BL/6N pregnant mice were administered control or protein restricted diets and subjected to either 100 <italic>μ</italic>g/Kg of dexamethasone sodium phosphate with normosaline or normosaline alone during late gestation (E10–E17). Nontreatment groups were also included. Brain samples were collected on embryonic day 17 and analyzed by mRNA microarray analysis. <italic>Results</italic>. Microarray analyses presented 332 significantly regulated genes. Overall, neurodevelopmental genes were overrepresented and a subset of 8 genes allowed treatment segregation through the hierarchical clustering method. The addition of stress or steroids greatly affected gene regulation through glucocorticoid receptor and stress signaling pathways. Furthermore, differences between dexamethasone-administered treatments implied a harmful effect during conditions of high stress. Microarray analysis was validated using qPCR. <italic>Conclusion</italic>. The effects of antenatal steroid therapy vary in fetuses according to maternal-fetal factors and environmental stimuli. Defining the key regulatory networks that signal either beneficial or damaging corticosteroid action would result in valuable adjustments to current treatment protocols.

DOI： 10.1155/2014/193816

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Other Link： http://downloads.hindawi.com/archive/2014/193816.xml

Language：English  

DOI： 10.1248/bpb.30.1080

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Language：English  

DOI： 10.1016/j.bbrc.2007.01.175

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Language：English  

DOI： 10.1016/j.bbamer.2007.01.005

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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