Promyelocytic leukemia nuclear bodies are predetermined processing sites for damaged DNA

Stig Ove Bøe*, Marte Haave, Åsne Jul-Larsen, Amra Grudic, Rolf Bjerkvig, Per Eystein Lønning

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    56 Citations (Scopus)

    Abstract

    The promyelocytic leukemia protein (PML) participates in several cellular functions, including transcriptional regulation, apoptosis and maintenance of genomic stability. A key feature of this protein is its ability to induce the assembly of nuclear compartments termed PML-nuclear bodies (PML-NBs). Here we show that these nuclear structures recruit single-stranded DNA (ssDNA) molecules in response to exogenous DNA damage. ssDNA was readily detected in PML-NBs within 1 hour following exposure of cells to UV light. Confocal real-time imaging of cells expressing YFP-tagged PML did not reveal de novo formation of new PML-NBs following UV-irradiation, which shows that ssDNA focus formation occurred within pre-existing PML-NBs. Moreover, siRNA-mediated depletion of PML prevented ssDNA focus formation and sensitized cells to UV-induced apoptosis. PML-dependent ssDNA focus formation was found to be particularly efficient during S-phase of the cell cycle, and PML-depleted cells became retarded in S-phase upon growth in the presence of etoposide. In addition, we found that caffeine and the poly(ADP-ribose) polymerase (PARP) inhibitor NU1027 enhanced UV-induced recruitment of ssDNA to PML-NBs. Together, our results show that PML-NBs have the capacity to accommodate DNA metabolic activities that are associated with processing of damaged DNA.

    Original languageEnglish
    Pages (from-to)3284-3295
    Number of pages12
    JournalJournal of Cell Science
    Volume119
    Issue number16
    DOIs
    Publication statusPublished - 15 Aug 2006

    Keywords

    • Bodies
    • DNA repair
    • DNA replication
    • PML

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