TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response
| Autor: | Lauren M. Young, Dylan A. Reid, Eli Rothenberg, Domenico Roberti, Michele Pagano, Daniel N. Meredith, Ayelet Star, Antonio Marzio, Pablo Pérez-Durán, Beatrix Ueberheide |
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| Přispěvatelé: | Young, Lauren M, Marzio, Antonio, Perez-Duran, Pablo, Reid, Dylan A, Meredith, Daniel N, Roberti, Domenico, Star, Ayelet, Rothenberg, Eli, Ueberheide, Beatrix, Pagano, Michele |
| Rok vydání: | 2015 |
| Předmět: |
DNA Repair
DNA damage DNA repair Timeless Poly ADP ribose polymerase Molecular Sequence Data Poly (ADP-Ribose) Polymerase-1 Cell Cycle Proteins Biology DNA-binding protein General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound PARP1 Cell Line Tumor Humans Amino Acid Sequence lcsh:QH301-705.5 Binding Sites Intracellular Signaling Peptides and Proteins Nuclear Proteins Molecular biology 3. Good health Cell biology DNA binding site DNA-Binding Proteins HEK293 Cells chemistry lcsh:Biology (General) Poly(ADP-ribose) Polymerases Carrier Proteins DNA DNA Damage Protein Binding |
| Zdroj: | Cell Reports, Vol 13, Iss 3, Pp 451-459 (2015) Cell reports |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.09.017 |
| Popis: | SUMMARY PARP1 is the main sensor of single- and double-strand breaks in DNA and, in building chains of poly(ADP-ribose), promotes the recruitment of many downstream signaling and effector proteins involved in the DNA damage response (DDR). We show a robust physical interaction between PARP1 and the replication fork protein TIMELESS, distinct from the known TIMELESS-TIPIN complex, which activates the intra-S phase checkpoint. TIMELESS recruitment to laser-induced sites of DNA damage is dependent on its binding to PARP1, but not PARP1 activity. We also find that the PARP1-TIMELESS complex contains a number of established PARP1 substrates, and TIMELESS mutants unable to bind PARP1 are impaired in their ability to bind PARP1 substrates. Further, PARP1 binding to certain substrates and their recruitment to DNA damage lesions is impaired by TIMELESS knockdown, and TIMELESS silencing significantly impairs DNA double-strand break repair. We hypothesize that TIMELESS cooperates in the PARP1-mediated DDR. Graphical abstract |
| Databáze: | OpenAIRE |
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