Acetylation regulates WRN catalytic activities and affects base excision DNA repair.
The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2276247?pdf=render |
| _version_ | 1819326994490327040 |
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| author | Meltem Muftuoglu Rika Kusumoto Elzbieta Speina Gad Beck Wen-Hsing Cheng Vilhelm A Bohr |
| author_facet | Meltem Muftuoglu Rika Kusumoto Elzbieta Speina Gad Beck Wen-Hsing Cheng Vilhelm A Bohr |
| author_sort | Meltem Muftuoglu |
| collection | DOAJ |
| description | The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription.Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol beta-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process.Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER. |
| first_indexed | 2024-12-24T13:03:47Z |
| format | Article |
| id | doaj.art-cfe2056cce0c4448a63199a85f0261cc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T13:03:47Z |
| publishDate | 2008-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cfe2056cce0c4448a63199a85f0261cc2022-12-21T16:54:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-04-0134e191810.1371/journal.pone.0001918Acetylation regulates WRN catalytic activities and affects base excision DNA repair.Meltem MuftuogluRika KusumotoElzbieta SpeinaGad BeckWen-Hsing ChengVilhelm A BohrThe Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription.Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol beta-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process.Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER.http://europepmc.org/articles/PMC2276247?pdf=render |
| spellingShingle | Meltem Muftuoglu Rika Kusumoto Elzbieta Speina Gad Beck Wen-Hsing Cheng Vilhelm A Bohr Acetylation regulates WRN catalytic activities and affects base excision DNA repair. PLoS ONE |
| title | Acetylation regulates WRN catalytic activities and affects base excision DNA repair. |
| title_full | Acetylation regulates WRN catalytic activities and affects base excision DNA repair. |
| title_fullStr | Acetylation regulates WRN catalytic activities and affects base excision DNA repair. |
| title_full_unstemmed | Acetylation regulates WRN catalytic activities and affects base excision DNA repair. |
| title_short | Acetylation regulates WRN catalytic activities and affects base excision DNA repair. |
| title_sort | acetylation regulates wrn catalytic activities and affects base excision dna repair |
| url | http://europepmc.org/articles/PMC2276247?pdf=render |
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