Publications by authors named "Halfdan Beck"

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.

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  • The study investigates the molecular processes that occur when DNA replication forks are disrupted, focusing on the role of the FBH1 helicase in this context.
  • It finds that cells lacking FBH1 are resistant to the effects of the replication inhibitor hydroxyurea and show reduced activation of the tumor suppressor p53, indicating less DNA damage.
  • The researchers also demonstrate that FBH1 works together with the MUS81 nuclease to create DNA double-strand breaks, which are necessary for killing cells under excessive replication stress.
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  • - Increased CDK activity due to WEE1 kinase inhibition causes a rapid rise in replication initiation, leading to problems like nucleotide shortages and slower replication fork speed.
  • - This slower fork speed results in DNA double-strand breaks, which can be mitigated by depleting CDT1 or adding nucleosides.
  • - WEE1 is crucial for managing the S-phase checkpoint in response to ionizing radiation, indicating its importance in maintaining genomic stability during replication.
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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 LEDGF impairs the recruitment of C-terminal binding protein interacting protein (CtIP) to DNA DSBs and the subsequent CtIP-dependent DNA-end resection.

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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.

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The yeast Saccharomyces kluyveri (Lachancea kluyveri), a far relative of Saccharomyces cerevisiae, is not a widely studied organism in the laboratory. However, significant contributions to the understanding of nucleic acid precursors degradation in eukaryotes have been made using this model organism. Here we review eukaryotic pyrimidine degradation with emphasis on the contributions made with S.

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