Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a “surveillant” of telomere replication, which orchestrates protein dynamics at proceeding replication fork.

PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment / Maresca, C.; Dello Stritto, A.; D’Angelo, C.; Petti, E.; Rizzo, A.; Vertecchi, E.; Berardinelli, F.; Bonanni, L.; Sgura, A.; Antoccia, A.; Graziani, G.; Biroccio &, A.; Salvati, E.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 6:1(2023). [10.1038/s42003-023-04596-6]

PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment

A. Dello Stritto;E. Vertecchi;A. Antoccia;
2023

Abstract

Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a “surveillant” of telomere replication, which orchestrates protein dynamics at proceeding replication fork.
2023
telomere, shelterin, TRF1, PARP1
01 Pubblicazione su rivista::01a Articolo in rivista
PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment / Maresca, C.; Dello Stritto, A.; D’Angelo, C.; Petti, E.; Rizzo, A.; Vertecchi, E.; Berardinelli, F.; Bonanni, L.; Sgura, A.; Antoccia, A.; Graziani, G.; Biroccio &, A.; Salvati, E.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 6:1(2023). [10.1038/s42003-023-04596-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1692532
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