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Citation
Yi, X., de Vries, H.I., Siudeja, K., Rana, A., Lemstra, W., Brunsting, J.F., Kok, R.M., Smulders, Y.M., Schaefer, M., Dijk, F., Shang, Y., Eggen, B.J., Kampinga, H.H., Sibon, O.C. (2009). Stwl modifies chromatin compaction and is required to maintain DNA integrity in the presence of perturbed DNA replication.  Mol. Biol. Cell 20(3): 983--994.
FlyBase ID
FBrf0215684
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC2633405 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Biol. Cell
    Title
    Molecular Biology of the Cell
    Publication Year
    1992-
    ISBN/ISSN
    1059-1524
    Data From Reference
    Genes (2)