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FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance
Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accura...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344513/ https://www.ncbi.nlm.nih.gov/pubmed/25662213 http://dx.doi.org/10.1093/nar/gkv076 |
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author | Baldeck, Nadège Janel-Bintz, Régine Wagner, Jérome Tissier, Agnès Fuchs, Robert P. Burkovics, Peter Haracska, Lajos Despras, Emmanuelle Bichara, Marc Chatton, Bruno Cordonnier, Agnès M. |
author_facet | Baldeck, Nadège Janel-Bintz, Régine Wagner, Jérome Tissier, Agnès Fuchs, Robert P. Burkovics, Peter Haracska, Lajos Despras, Emmanuelle Bichara, Marc Chatton, Bruno Cordonnier, Agnès M. |
author_sort | Baldeck, Nadège |
collection | PubMed |
description | Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Polη deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF(483–484) amino acids in the human Polη (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase δ, both in vitro and in vivo. Mutating this motif impairs Polη function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Polη, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Polη, necessary for the Polη/POLD2 interaction, is required for the establishment of an efficient TLS complex. |
format | Online Article Text |
id | pubmed-4344513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43445132015-03-17 FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance Baldeck, Nadège Janel-Bintz, Régine Wagner, Jérome Tissier, Agnès Fuchs, Robert P. Burkovics, Peter Haracska, Lajos Despras, Emmanuelle Bichara, Marc Chatton, Bruno Cordonnier, Agnès M. Nucleic Acids Res Genome Integrity, Repair and Replication Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Polη deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF(483–484) amino acids in the human Polη (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase δ, both in vitro and in vivo. Mutating this motif impairs Polη function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Polη, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Polη, necessary for the Polη/POLD2 interaction, is required for the establishment of an efficient TLS complex. Oxford University Press 2015-02-27 2015-02-06 /pmc/articles/PMC4344513/ /pubmed/25662213 http://dx.doi.org/10.1093/nar/gkv076 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Baldeck, Nadège Janel-Bintz, Régine Wagner, Jérome Tissier, Agnès Fuchs, Robert P. Burkovics, Peter Haracska, Lajos Despras, Emmanuelle Bichara, Marc Chatton, Bruno Cordonnier, Agnès M. FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance |
title | FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance |
title_full | FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance |
title_fullStr | FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance |
title_full_unstemmed | FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance |
title_short | FF(483–484) motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance |
title_sort | ff(483–484) motif of human polη mediates its interaction with the pold2 subunit of polδ and contributes to dna damage tolerance |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344513/ https://www.ncbi.nlm.nih.gov/pubmed/25662213 http://dx.doi.org/10.1093/nar/gkv076 |
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