02 May 2003
Functional interaction between PARP-2 and TRF2: PARP activity negatively regulates TRF2
F. Dantzer, J. Ame, I. Jaco, I. Schulz, M. Giraud-Panis, M. Blasco, E. Gilson, J. Menissier-de Murcia, G. de Murcia, V. SchreiberMed Sci Monit 2003; 9(1): 20-0 :: ID: 15067
Abstract
The DNA-damage dependent poly(ADP-ribose) polymerase-2 (PARP-2) is together with PARP-1 an active player of the base excision repair process thus defining its key role in genome surveillance and protection [1] Telomeres are specialized DNA-protein structures that protect chromosome ends from being recognized and processed as DNA strand breaks. In mammalian, telomere protection depends on the T2AG3 repeat binding protein TRF2, which has been shown to remodel telomeres into large duplex loops (t-loops) [2,3].We present evidence for the possible involvement of PARP-2 in the maintenance of telomere integrity. We show that PARP-2 physically binds to TRF2 with high affinity. The association of both proteins requires the N-terminal domain of PARP-2 and the myb domain of TRF2. Both partners colocalize at promyelocytic leukemia bodies in immortalized telomerase-negative cells. In addition, our data show that PARP activity regulates the DNA binding activity of TRF2 via both a covalent heteromodification of the dimerization domain of TRF2 and a non covalent binding of poly(ADP-ribose) to the myb domain of TRF2. PARP-2–/– primary cells show normal telomere length as well as normal telomerase activity as compared with wild-type cells but display a spontaneously increased frequency of ends lacking detectable T2 AG3 repeats. Altogether, these results suggest that PARP-2 activity function at telomeres, possibly by modulating t-loop formation in response to DNA damage.References: 1.Schreiber V et al: J Biol Chem, 2002; 277: 23028-23036 2.van Steensel B et al: Cell, 1998; 92: 401-413 3.Griffith JD et al: Cell, 1999; 97: 503-514
Keywords: Poly(ADP-ribose) polymerase-2, TRF2, telomere integrity, cellular response to DNA damage
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