EMBO Reports
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Werner's syndrome protein (WRN) migrates Holliday junctions and co‐localizes with RPA upon replication arrest Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3′–5′ DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (BLM ). In this work, we show that WRN promotes the ATP‐dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S‐phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single‐stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates.
EMBO Reports - Tập 1 Số 1 - Trang 80-84 - 2000
A reciprocal repression between ZEB1 and members of the miR‐200 family promotes EMT and invasion in cancer cells The embryonic programme ‘epithelial–mesenchymal transition’ (EMT) is thought to promote malignant tumour progression. The transcriptional repressor zinc‐finger E‐box binding homeobox 1 (ZEB1) is a crucial inducer of EMT in various human tumours, and was recently shown to promote invasion and metastasis of tumour cells. Here, we report that ZEB1 directly suppresses transcription of microRNA‐200 family members miR‐141 and miR‐200c, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT activators transforming growth factor β2 and ZEB1 are the predominant targets downregulated by these microRNAs. These results indicate that ZEB1 triggers an microRNA‐mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells. Alternatively, depending on the environmental trigger, this loop might switch and induce epithelial differentiation, and thus explain the strong intratumorous heterogeneity observed in many human cancers.
EMBO Reports - Tập 9 Số 6 - Trang 582-589 - 2008
Structure of the ubiquitin‐binding zinc finger domain of human DNA Y‐polymerase η
EMBO Reports - Tập 8 Số 3 - Trang 247-251 - 2007
NMR structure of the bovine prion protein isolated from healthy calf brains NMR structures of recombinant prion proteins from various species expressed in Escherichia coli have been solved during the past years, but the fundamental question of the relevancy of these data relative to the naturally occurring forms of the prion protein has not been directly addressed. Here, we present a comparison of the cellular form of the bovine prion protein isolated and purified from healthy calf brains without use of detergents, so that it contains the two carbohydrate moieties and the part of the GPI anchor that is maintained after enzymatic cleavage of the glycerolipid moiety, with the recombinant bovine prion protein expressed in E. coli . We show by circular dichroism and 1 H‐NMR spectroscopy that the three‐dimensional structure and the thermal stability of the natural glycoprotein and the recombinant polypeptide are essentially identical. This result indicates possible functional roles of the glycosylation of prion proteins in healthy organisms, and provides a platform and validation for future work on the structural biology of prion proteins, which will have to rely primarily on the use of recombinant polypeptides.
EMBO Reports - Tập 5 Số 12 - Trang 1159-1164 - 2004
Psychrophilic microorganisms: challenges for life The ability of psychrophiles to survive and proliferate at low temperatures implies that they have overcome key barriers inherent to permanently cold environments. These challenges include: reduced enzyme activity; decreased membrane fluidity; altered transport of nutrients and waste products; decreased rates of transcription, translation and cell division; protein cold‐denaturation; inappropriate protein folding; and intracellular ice formation. Cold‐adapted organisms have successfully evolved features, genotypic and/or phenotypic, to surmount the negative effects of low temperatures and to enable growth in these extreme environments. In this review, we discuss the current knowledge of these adaptations as gained from extensive biochemical and biophysical studies and also from genomics and proteomics.
EMBO Reports - Tập 7 Số 4 - Trang 385-389 - 2006
Daughter‐specific repression of <i>Saccharomyces cerevisiae HO</i>: Ash1 is the commander The GATA‐1‐like factor Ash1 is a repressor of the HO gene, which encodes an endonuclease that is responsible for mating‐type switching in the yeast Saccharomyces cerevisiae . A multi‐step programme, which involves a macromolecular protein complex, the secondary structure of ASH1 mRNA and the cell cytoskeleton, enables Ash1 to asymmetrically localize to the daughter cell nucleus in late anaphase and to repress HO transcription. The resulting Ash1 activity prevents the daughter cell from switching mating type. How does Ash1 inhibit transcription of HO exclusively in the daughter cell? In this review, a speculative model is proposed and discussed. Through its action as a daughter‐specific repressor, Ash1 can be considered to be an ancestral regulator of cell fate in eukaryotes.
EMBO Reports - Tập 5 Số 10 - Trang 953-957 - 2004
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