The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 25 Jul 2006
doi: 10.1242/jcs.03068
Research Article
Promyelocytic leukemia nuclear bodies are predetermined processing sites for damaged DNA
Stig Ove Bøe*,
Marte Haave,
Åsne Jul-Larsen,
Amra Grudic,
Rolf Bjerkvig,
and
Per Eystein Lønning
* Author for correspondence (e-mail: stig.boe{at}vir.uib.no)
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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
Y.-L. Chung and T.-Y. Tsai
Promyelocytic Leukemia Nuclear Bodies Link the DNA Damage Repair Pathway with Hepatitis B Virus Replication: Implications for Hepatitis B Virus Exacerbation during Chemotherapy and Radiotherapy
Mol. Cancer Res.,
October 1, 2009;
7(10):
1672 - 1685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Weidtkamp-Peters, T. Lenser, D. Negorev, N. Gerstner, T. G. Hofmann, G. Schwanitz, C. Hoischen, G. Maul, P. Dittrich, and P. Hemmerich
Dynamics of component exchange at PML nuclear bodies
J. Cell Sci.,
August 15, 2008;
121(16):
2731 - 2743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhao, R. J. Madden-Fuentes, B. X. Lou, J. M. Pipas, J. Gerhardt, C. J. Rigell, and E. Fanning
Ataxia Telangiectasia-Mutated Damage-Signaling Kinase- and Proteasome-Dependent Destruction of Mre11-Rad50-Nbs1 Subunits in Simian Virus 40-Infected Primate Cells
J. Virol.,
June 1, 2008;
82(11):
5316 - 5328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Grudic, A. Jul-Larsen, S. J. Haring, M. S. Wold, P. E. Lonning, R. Bjerkvig, and S. O. Boe
Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres
Nucleic Acids Res.,
December 18, 2007;
35(21):
7267 - 7278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Liontos, M. Koutsami, M. Sideridou, K. Evangelou, D. Kletsas, B. Levy, A. Kotsinas, O. Nahum, V. Zoumpourlis, M. Kouloukoussa, et al.
Deregulated Overexpression of hCdt1 and hCdc6 Promotes Malignant Behavior
Cancer Res.,
November 15, 2007;
67(22):
10899 - 10909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Condemine, Y. Takahashi, M. Le Bras, and H. de The
A nucleolar targeting signal in PML-I addresses PML to nucleolar caps in stressed or senescent cells
J. Cell Sci.,
September 15, 2007;
120(18):
3219 - 3227.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
