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First published online 25 July 2006
doi: 10.1242/jcs.03068
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Research Article |
1 Section of Oncology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
2 Section of Anatomy and Cell Biology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009, Bergen, Norway
3 NorLux, Neuro-Oncology, Centre Recherche Public Santé, Luxembourg
* Author for correspondence (e-mail: stig.boe{at}vir.uib.no)
Accepted 25 May 2006
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.
Key words: PML, DNA repair, DNA replication, Bodies
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