HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease
© 2020, The Author(s). DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/134543 |
| _version_ | 1826188290286419968 |
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| author | Pao, Ping-Chieh Patnaik, Debasis Watson, L Ashley Gao, Fan Pan, Ling Wang, Jun Adaikkan, Chinnakkaruppan Penney, Jay Cam, Hugh P Huang, Wen-Chin Pantano, Lorena Lee, Audrey Nott, Alexi Phan, Trongha X Gjoneska, Elizabeta Elmsaouri, Sara Haggarty, Stephen J Tsai, Li-Huei |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Pao, Ping-Chieh Patnaik, Debasis Watson, L Ashley Gao, Fan Pan, Ling Wang, Jun Adaikkan, Chinnakkaruppan Penney, Jay Cam, Hugh P Huang, Wen-Chin Pantano, Lorena Lee, Audrey Nott, Alexi Phan, Trongha X Gjoneska, Elizabeta Elmsaouri, Sara Haggarty, Stephen J Tsai, Li-Huei |
| author_sort | Pao, Ping-Chieh |
| collection | MIT |
| description | © 2020, The Author(s). DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration. |
| first_indexed | 2024-09-23T07:57:25Z |
| format | Article |
| id | mit-1721.1/134543 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T07:57:25Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1345432023-12-22T19:08:37Z HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease Pao, Ping-Chieh Patnaik, Debasis Watson, L Ashley Gao, Fan Pan, Ling Wang, Jun Adaikkan, Chinnakkaruppan Penney, Jay Cam, Hugh P Huang, Wen-Chin Pantano, Lorena Lee, Audrey Nott, Alexi Phan, Trongha X Gjoneska, Elizabeta Elmsaouri, Sara Haggarty, Stephen J Tsai, Li-Huei Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences © 2020, The Author(s). DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration. 2021-10-27T20:05:29Z 2021-10-27T20:05:29Z 2020 2021-03-23T18:10:15Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134543 en 10.1038/S41467-020-16361-Y Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Pao, Ping-Chieh Patnaik, Debasis Watson, L Ashley Gao, Fan Pan, Ling Wang, Jun Adaikkan, Chinnakkaruppan Penney, Jay Cam, Hugh P Huang, Wen-Chin Pantano, Lorena Lee, Audrey Nott, Alexi Phan, Trongha X Gjoneska, Elizabeta Elmsaouri, Sara Haggarty, Stephen J Tsai, Li-Huei HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease |
| title | HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease |
| title_full | HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease |
| title_fullStr | HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease |
| title_full_unstemmed | HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease |
| title_short | HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease |
| title_sort | hdac1 modulates ogg1 initiated oxidative dna damage repair in the aging brain and alzheimer s disease |
| url | https://hdl.handle.net/1721.1/134543 |
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