Stwl Modifies Chromatin Compaction and Is Required to Maintain DNA Integrity in the Presence of Perturbed DNA Replication

Xia Yi, Hilda I. de Vries, Katarzyna Siudeja, Anil Rana, Willy Lemstra, Jeanette F. Brunsting, Rob M. Kok, Yvo M. Smulders, Matthias Schaefer, Freark Dijk, Yongfeng Shang, Bart J.L. Eggen, Harm H. Kampinga, Ody C.M. Sibon

    Research output: Contribution to journalArticleAcademicpeer-review

    13 Citations (Scopus)
    290 Downloads (Pure)

    Abstract

    Hydroxyurea, a well-known DNA replication inhibitor, induces cell cycle arrest and intact checkpoint functions are required to survive DNA replication stress induced by this genotoxic agent. Perturbed DNA synthesis also results in elevated levels of DNA damage. It is unclear how organisms prevent accumulation of this type of DNA damage that coincides with hampered DNA synthesis. Here, we report the identification of stonewall ( stwl) as a novel hydroxyurea-hypersensitive mutant. We demonstrate that Stwl is required to prevent accumulation of DNA damage induced by hydroxyurea; yet, Stwl is not involved in S/M checkpoint regulation. We show that Stwl is a heterochromatin-associated protein with transcription-repressing capacities. In stwl mutants, levels of trimethylated H3K27 and H3K9 ( two hallmarks of silent chromatin) are decreased. Our data provide evidence for a Stwl-dependent epigenetic mechanism that is involved in the maintenance of the normal balance between euchromatin and heterochromatin and that is required to prevent accumulation of DNA damage in the presence of DNA replication stress.

    Original languageEnglish
    Pages (from-to)983-994
    Number of pages12
    JournalMolecular Biology of the Cell
    Volume20
    Issue number3
    DOIs
    Publication statusPublished - Feb-2009

    Keywords

    • STRAND BREAK REPAIR
    • HISTONE H2AX PHOSPHORYLATION
    • CELL-CYCLE CHECKPOINTS
    • DROSOPHILA-MELANOGASTER
    • MAMMALIAN-CELLS
    • SACCHAROMYCES-CEREVISIAE
    • MIDBLASTULA TRANSITION
    • SENSITIVE MUTATIONS
    • DAMAGE CHECKPOINT
    • GENE

    Cite this