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MBC in Press, published online ahead of print January 25, 2006
Mol. Biol. Cell 10.1091/mbc.E05-07-0672

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Submitted on July 25, 2005
Revised on January 11, 2006
Accepted on January 18, 2006

PARP1 Is a TRF2-associated Poly(ADP-Ribose)Polymerase and Protects Eroded Telomeres

Marla Gomez,* Jun Wu,* Valérie Schreiber,{dagger} John Dunlap,{ddagger} Françoise Dantzer,{dagger} Yisong Wang,*{sect} and Yie Liu*{sect}

*Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6445; {dagger}Département Intégrité du Génome de l’UMR7175-LC1 du CNRS, Université Louis Pasteur, Ecole Supérieure de Biotechnologie de Strasbourg, 67412 Illkirch Cedex, France; {ddagger}Microscopy Facility, Division of Biology, The University of Tennessee, Knoxville, TN 37996; {sect}Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN 37996-0840

Monitoring Editor: A. Gregory Matera

Poly(ADP-ribose) polymerase 1 (PARP1) is well characterized for its role in base excision repair (BER), where it is activated by and binds to DNA breaks and catalyzes the poly(ADP-ribosyl)ation of several substrates involved in DNA damage repair. Here we demonstrate that PARP1 associates with telomere repeat binding factor 2 (TRF2) and is capable of poly(ADP-ribosyl)ation of TRF2, which affects binding of TRF2 to telomeric DNA. Immunostaining of interphase cells or metaphase spreads shows that PARP1 is detected sporadically at normal telomeres, but it appears preferentially at eroded telomeres caused by telomerase deficiency or damaged telomeres induced by DNA damaging reagents. Although PARP1 is dispensable in the capping of normal telomeres, Parp1 deficiency leads to an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA in primary murine cells after induction of DNA damage. Our results suggest that upon DNA damage, PARP1 is recruited to damaged telomeres where it can help protect telomeres against chromosome end-to-end fusions and genomic instability.


Address correspondence to: Yisong Wang (ywa{at}ornl.gov) or Yie Liu (liuy3{at}ornl.gov)




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