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Regulation of PCNA polyubiquitination in human cells

BACKGROUND: The ubiquitin-based molecular switch dictating error free versus error prone repair has been conserved throughout eukaryotic evolution. A central component of this switch is the homotrimeric clamp PCNA, which is ubiquitinated in response to genotoxic stress allowing recovery of replicati...

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Autores principales: Brun, Jan, Chiu, Roland K, Wouters, Bradly G, Gray, Douglas A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867771/
https://www.ncbi.nlm.nih.gov/pubmed/20353596
http://dx.doi.org/10.1186/1756-0500-3-85
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author Brun, Jan
Chiu, Roland K
Wouters, Bradly G
Gray, Douglas A
author_facet Brun, Jan
Chiu, Roland K
Wouters, Bradly G
Gray, Douglas A
author_sort Brun, Jan
collection PubMed
description BACKGROUND: The ubiquitin-based molecular switch dictating error free versus error prone repair has been conserved throughout eukaryotic evolution. A central component of this switch is the homotrimeric clamp PCNA, which is ubiquitinated in response to genotoxic stress allowing recovery of replication forks blocked at sites of DNA damage. The particulars of PCNA ubiquitination have been elucidated in yeast and to a further extent recently in human cells. However, gaps in the detailed mechanism and regulation of PCNA polyubiquitination still persist in human cells. FINDINGS: We expand upon several studies and show that PCNA is polyubiquitnated in normal skin fibroblasts, and that this ubiquitination is dependant on RAD18. Furthermore we define the types of DNA damage that induce ubiquitination on PCNA. Cisplatin, methylmethane sulphonate and benzo(a)pyrene-diol-epoxide induce the polyubiquitination of PCNA to the same extent as UV while polyubiquitination is not detected after X-ray treatment. Moreover, we show that ubiquitination of PCNA is not regulated by cell cycle checkpoint kinases ATM-Chk2 or ATR-Chk1. Significantly, we report that PCNA polyubiquitination is negatively regulated by USP1. CONCLUSIONS: Our results demonstrate the importance of PCNA polyubiquitination in human cells and define the key regulator of this ubiquitination.
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spelling pubmed-28677712010-05-12 Regulation of PCNA polyubiquitination in human cells Brun, Jan Chiu, Roland K Wouters, Bradly G Gray, Douglas A BMC Res Notes Short Report BACKGROUND: The ubiquitin-based molecular switch dictating error free versus error prone repair has been conserved throughout eukaryotic evolution. A central component of this switch is the homotrimeric clamp PCNA, which is ubiquitinated in response to genotoxic stress allowing recovery of replication forks blocked at sites of DNA damage. The particulars of PCNA ubiquitination have been elucidated in yeast and to a further extent recently in human cells. However, gaps in the detailed mechanism and regulation of PCNA polyubiquitination still persist in human cells. FINDINGS: We expand upon several studies and show that PCNA is polyubiquitnated in normal skin fibroblasts, and that this ubiquitination is dependant on RAD18. Furthermore we define the types of DNA damage that induce ubiquitination on PCNA. Cisplatin, methylmethane sulphonate and benzo(a)pyrene-diol-epoxide induce the polyubiquitination of PCNA to the same extent as UV while polyubiquitination is not detected after X-ray treatment. Moreover, we show that ubiquitination of PCNA is not regulated by cell cycle checkpoint kinases ATM-Chk2 or ATR-Chk1. Significantly, we report that PCNA polyubiquitination is negatively regulated by USP1. CONCLUSIONS: Our results demonstrate the importance of PCNA polyubiquitination in human cells and define the key regulator of this ubiquitination. BioMed Central 2010-03-30 /pmc/articles/PMC2867771/ /pubmed/20353596 http://dx.doi.org/10.1186/1756-0500-3-85 Text en Copyright ©2010 Gray et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Report
Brun, Jan
Chiu, Roland K
Wouters, Bradly G
Gray, Douglas A
Regulation of PCNA polyubiquitination in human cells
title Regulation of PCNA polyubiquitination in human cells
title_full Regulation of PCNA polyubiquitination in human cells
title_fullStr Regulation of PCNA polyubiquitination in human cells
title_full_unstemmed Regulation of PCNA polyubiquitination in human cells
title_short Regulation of PCNA polyubiquitination in human cells
title_sort regulation of pcna polyubiquitination in human cells
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867771/
https://www.ncbi.nlm.nih.gov/pubmed/20353596
http://dx.doi.org/10.1186/1756-0500-3-85
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