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First published online December 22, 2004
doi: 10.1242/10.1242/jcs.01606
Research Article |
1 UPR 9003 du Centre National de la Recherche Scientifique. Laboratoire conventionné avec le Commissariat à l'Energie Atomique, Université Louis Pasteur, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP10413, 67412 Illkirch, France
2 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 163, 67404 Illkirch, France
* Author for correspondence (e-mail: schreibe{at}esbs.u-strasbg.fr)
Accepted 25 October 2004
The DNA damage-dependent poly(ADP-ribose) polymerases-1 and -2 (PARP-1 and PARP-2) are survival factors that share overlapping functions in the detection, signaling and repair of DNA strand breaks resulting from genotoxic lesions in mammalian cells. Here we show that PARP-1 and PARP-2 subnuclear distributions partially overlap, with both proteins accumulating within the nucleolus independently of each other. PARP-2 is enriched within the whole nucleolus and partially colocalizes with the nucleolar factor nucleophosmin/B23. We have identified a nuclear localization signal and a nucleolar localization signal within the N-terminal domain of PARP-2. PARP-2, like PARP-1, interacts with B23 through its N-terminal DNA binding domain. This association is constitutive and does not depend on either PARP activity or ribosomal transcription, but is prevented by mutation of the nucleolar localization signal of PARP-2. PARP-1 and PARP-2, together with B23, are delocalized from the nucleolus upon RNA polymerase I inhibition whereas the nucleolar accumulation of all three proteins is only moderately affected upon oxidative or alkylated DNA damage. Finally, we show that murine fibroblasts deficient in PARP-1 or PARP-2 are not affected in the transcription of ribosomal RNAs. Taken together, these results suggest that the biological role of PARP-1 and PARP-2 within the nucleolus relies on functional nucleolar transcription, without any obvious implication of either PARP on this major nucleolar process.
Key words: Cellular response to DNA damage, Poly(ADP-ribosyl)ation, PARP homologues, Nuclear and nucleolar localization signals
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