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CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis
The proliferating cell nuclear antigen (PCNA) protein serves as a molecular platform recruiting and coordinating the activity of factors involved in multiple deoxyribonucleic acid (DNA) transactions. To avoid dangerous genome instability, it is necessary to prevent excessive retention of PCNA on chr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117764/ https://www.ncbi.nlm.nih.gov/pubmed/24939902 http://dx.doi.org/10.1093/nar/gku533 |
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author | Cazzalini, Ornella Sommatis, Sabrina Tillhon, Micol Dutto, Ilaria Bachi, Angela Rapp, Alexander Nardo, Tiziana Scovassi, A. Ivana Necchi, Daniela Cardoso, M. Cristina Stivala, Lucia A. Prosperi, Ennio |
author_facet | Cazzalini, Ornella Sommatis, Sabrina Tillhon, Micol Dutto, Ilaria Bachi, Angela Rapp, Alexander Nardo, Tiziana Scovassi, A. Ivana Necchi, Daniela Cardoso, M. Cristina Stivala, Lucia A. Prosperi, Ennio |
author_sort | Cazzalini, Ornella |
collection | PubMed |
description | The proliferating cell nuclear antigen (PCNA) protein serves as a molecular platform recruiting and coordinating the activity of factors involved in multiple deoxyribonucleic acid (DNA) transactions. To avoid dangerous genome instability, it is necessary to prevent excessive retention of PCNA on chromatin. Although PCNA functions during DNA replication appear to be regulated by different post-translational modifications, the mechanism regulating PCNA removal and degradation after nucleotide excision repair (NER) is unknown. Here we report that CREB-binding protein (CBP), and less efficiently p300, acetylated PCNA at lysine (Lys) residues Lys13,14,77 and 80, to promote removal of chromatin-bound PCNA and its degradation during NER. Mutation of these residues resulted in impaired DNA replication and repair, enhanced the sensitivity to ultraviolet radiation, and prevented proteolytic degradation of PCNA after DNA damage. Depletion of both CBP and p300, or failure to load PCNA on DNA in NER deficient cells, prevented PCNA acetylation and degradation, while proteasome inhibition resulted in accumulation of acetylated PCNA. These results define a CBP and p300-dependent mechanism for PCNA acetylation after DNA damage, linking DNA repair synthesis with removal of chromatin-bound PCNA and its degradation, to ensure genome stability. |
format | Online Article Text |
id | pubmed-4117764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41177642014-08-15 CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis Cazzalini, Ornella Sommatis, Sabrina Tillhon, Micol Dutto, Ilaria Bachi, Angela Rapp, Alexander Nardo, Tiziana Scovassi, A. Ivana Necchi, Daniela Cardoso, M. Cristina Stivala, Lucia A. Prosperi, Ennio Nucleic Acids Res Genome Integrity, Repair and Replication The proliferating cell nuclear antigen (PCNA) protein serves as a molecular platform recruiting and coordinating the activity of factors involved in multiple deoxyribonucleic acid (DNA) transactions. To avoid dangerous genome instability, it is necessary to prevent excessive retention of PCNA on chromatin. Although PCNA functions during DNA replication appear to be regulated by different post-translational modifications, the mechanism regulating PCNA removal and degradation after nucleotide excision repair (NER) is unknown. Here we report that CREB-binding protein (CBP), and less efficiently p300, acetylated PCNA at lysine (Lys) residues Lys13,14,77 and 80, to promote removal of chromatin-bound PCNA and its degradation during NER. Mutation of these residues resulted in impaired DNA replication and repair, enhanced the sensitivity to ultraviolet radiation, and prevented proteolytic degradation of PCNA after DNA damage. Depletion of both CBP and p300, or failure to load PCNA on DNA in NER deficient cells, prevented PCNA acetylation and degradation, while proteasome inhibition resulted in accumulation of acetylated PCNA. These results define a CBP and p300-dependent mechanism for PCNA acetylation after DNA damage, linking DNA repair synthesis with removal of chromatin-bound PCNA and its degradation, to ensure genome stability. Oxford University Press 2014-09-01 2014-06-17 /pmc/articles/PMC4117764/ /pubmed/24939902 http://dx.doi.org/10.1093/nar/gku533 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Cazzalini, Ornella Sommatis, Sabrina Tillhon, Micol Dutto, Ilaria Bachi, Angela Rapp, Alexander Nardo, Tiziana Scovassi, A. Ivana Necchi, Daniela Cardoso, M. Cristina Stivala, Lucia A. Prosperi, Ennio CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis |
title | CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis |
title_full | CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis |
title_fullStr | CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis |
title_full_unstemmed | CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis |
title_short | CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis |
title_sort | cbp and p300 acetylate pcna to link its degradation with nucleotide excision repair synthesis |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117764/ https://www.ncbi.nlm.nih.gov/pubmed/24939902 http://dx.doi.org/10.1093/nar/gku533 |
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