Halfdan Beck

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Lens epithelium–derived growth factor p75 splice variant (LEDGF) is a chromatin-binding protein known for its antiapoptotic activity and ability to direct human immunodeficiency virus into active transcription units. Here we show that LEDGF promotes the repair of DNA double-strand breaks (DSBs) by the homologous recombination repair pathway. Depletion of(More)
Activation of oncogenes or inhibition of WEE1 kinase deregulates cyclin-dependent kinase (CDK) activity and leads to replication stress; however, the underlying mechanism is not understood. We now show that elevation of CDK activity by inhibition of WEE1 kinase rapidly increases initiation of replication. This leads to nucleotide shortage and reduces(More)
Maintenance of genome integrity is of critical importance to cells. To identify key regulators of genomic integrity, we screened a human cell line with a kinome small interfering RNA library. WEE1, a major regulator of mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative regulators of CDK1 and -2. Strikingly, WEE1(More)
Patterns of drug sensitivities in relation to topoisomerase II gene expression and activity were studied in eight human lung cancer cell lines not selected in vitro for drug resistance. The cytotoxicities of doxorubicin, etoposide, teniposide, cisplatin, camptothecin, and 5-fluorouracil were measured and, remarkably, these unselected cell lines were shown(More)
The molecular events occurring following the disruption of DNA replication forks are poorly characterized, despite extensive use of replication inhibitors such as hydroxyurea in the treatment of malignancies. Here, we identify a key role for the FBH1 helicase in mediating DNA double-strand break formation following replication inhibition. We show that(More)
Actin, arranged for example in stress fibres, provides a fundamental cytoskeletal framework function to all cell types. Notably, there is now mounting evidence that, in addition to cytoplasmic cytoskeletal regulation, actin treadmilling provides a signal modulating nuclear gene expression. In altering gene regulation, cytoplasmic and most likely also a(More)
Pyrimidines are important nucleic acid precursors which are constantly synthesized, degraded, and rebuilt in the cell. Four degradation pathways, two of which are found in eukaryotes, have been described. One of them, the URC pathway, has been initially discovered in our laboratory in the yeast Lachancea kluyveri. Here, we present the global changes in gene(More)
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