Proteomic Profiling Reveals a Specific Role for Translesion DNA Polymerase η in the Alternative Lengthening of Telomeres
| Autor: | Callen T. Wallace, Patricia L. Opresko, Marietta Y.W.T. Lee, Jean-Sébastien Hoffmann, Elodie Bournique, Jonathan Barroso-González, Valérie Bergoglio, Arindam Bose, Justin L. Roncaioli, Laura García-Expósito, Simon C. Watkins, Sufang Zhang, Roderick J. O’Sullivan |
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| Přispěvatelé: | Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Key Laboratory of Forest Protection of State Forest Administration, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
DNA Replication
Proteomics 0301 basic medicine Telomere Recombination Telomerase DNA polymerase DNA repair [SDV]Life Sciences [q-bio] Mitosis DNA-Directed DNA Polymerase DNA polymerase eta Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences cancer Humans Biotinylation BioID D-loop translesion DNA synthesis lcsh:QH301-705.5 Polymerase ComputingMilieux_MISCELLANEOUS DNA Polymerase III biology DNA synthesis Recombinational DNA Repair Telomere Homeostasis DNA Telomere Molecular biology polymerase 030104 developmental biology lcsh:Biology (General) biology.protein HeLa Cells |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2016, 17 (7), pp.1858-1871. ⟨10.1016/j.celrep.2016.10.048⟩ Cell reports Cell Reports, Vol 17, Iss 7, Pp 1858-1871 (2016) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Cancer cells rely on the activation of telomerase or the alternative lengthening of telomeres (ALT) pathways for telomere maintenance and survival. ALT involves homologous recombination (HR)-dependent exchange and/or HR-associated synthesis of telomeric DNA. Utilizing proximity-dependent biotinylation (BioID), we sought to determine the proteome of telomeres in cancer cells that employ these distinct telomere elongation mechanisms. Our analysis reveals that multiple DNA repair networks converge at ALT telomeres. These include the specialized translesion DNA synthesis (TLS) proteins FANCJ-RAD18-PCNA and, most notably, DNA polymerase eta (Polη). We observe that the depletion of Polη leads to increased ALT activity and late DNA polymerase δ (Polδ)-dependent synthesis of telomeric DNA in mitosis. We propose that Polη fulfills an important role in managing replicative stress at ALT telomeres, maintaining telomere recombination at tolerable levels and stimulating DNA synthesis by Polδ. Graphical Abstract |
| Databáze: | OpenAIRE |
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