Promyelocytic leukemia nuclear bodies are predetermined processing sites for damaged DNA

J Cell Sci. 2006 Aug 15;119(Pt 16):3284-95. doi: 10.1242/jcs.03068. Epub 2006 Jul 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Caffeine / pharmacology
  • Cell Nucleus Structures / genetics
  • Cell Nucleus Structures / metabolism*
  • Cells, Cultured
  • Central Nervous System Stimulants / pharmacology
  • DNA Damage / drug effects
  • DNA Damage / radiation effects*
  • DNA Repair*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / radiation effects
  • Humans
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • RNA, Small Interfering / pharmacology
  • S Phase / drug effects
  • S Phase / radiation effects
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Ultraviolet Rays
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism
  • Umbilical Veins / radiation effects
  • Zinc Fingers


  • Central Nervous System Stimulants
  • DNA, Neoplasm
  • DNA, Single-Stranded
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • RNA, Small Interfering
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Caffeine