Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair
The nuclear lamins are essential for various molecular events in the nucleus, such as chromatin organization, DNA replication, and provision of mechanical support. A specific point mutation in the LMNA gene creates a truncated prelamin A termed progerin, causing Hutchinson-Gilford progeria syndrome...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715011456 |
| _version_ | 1819080924462055424 |
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| author | Shrestha Ghosh Baohua Liu Yi Wang Quan Hao Zhongjun Zhou |
| author_facet | Shrestha Ghosh Baohua Liu Yi Wang Quan Hao Zhongjun Zhou |
| author_sort | Shrestha Ghosh |
| collection | DOAJ |
| description | The nuclear lamins are essential for various molecular events in the nucleus, such as chromatin organization, DNA replication, and provision of mechanical support. A specific point mutation in the LMNA gene creates a truncated prelamin A termed progerin, causing Hutchinson-Gilford progeria syndrome (HGPS). SIRT6 deficiency leads to defective genomic maintenance and accelerated aging similar to HGPS, suggesting a potential link between lamin A and SIRT6. Here, we report that lamin A is an endogenous activator of SIRT6 and facilitates chromatin localization of SIRT6 upon DNA damage. Lamin A promotes SIRT6-dependent DNA-PKcs (DNA-PK catalytic subunit) recruitment to chromatin, CtIP deacetylation, and PARP1 mono-ADP ribosylation in response to DNA damage. The presence of progerin jeopardizes SIRT6 activation and compromises SIRT6-mediated molecular events in response to DNA damage. These data reveal a critical role for lamin A in regulating SIRT6 activities, suggesting that defects in SIRT6 functions contribute to impaired DNA repair and accelerated aging in HGPS. |
| first_indexed | 2024-12-21T19:52:37Z |
| format | Article |
| id | doaj.art-29e25a0bd41a4025befbc7928f026716 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T19:52:37Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-29e25a0bd41a4025befbc7928f0267162022-12-21T18:52:10ZengElsevierCell Reports2211-12472015-11-011371396140610.1016/j.celrep.2015.10.006Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA RepairShrestha Ghosh0Baohua Liu1Yi Wang2Quan Hao3Zhongjun Zhou4School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pok Fu Lam, Hong KongSchool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pok Fu Lam, Hong KongSchool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pok Fu Lam, Hong KongSchool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pok Fu Lam, Hong KongSchool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pok Fu Lam, Hong KongThe nuclear lamins are essential for various molecular events in the nucleus, such as chromatin organization, DNA replication, and provision of mechanical support. A specific point mutation in the LMNA gene creates a truncated prelamin A termed progerin, causing Hutchinson-Gilford progeria syndrome (HGPS). SIRT6 deficiency leads to defective genomic maintenance and accelerated aging similar to HGPS, suggesting a potential link between lamin A and SIRT6. Here, we report that lamin A is an endogenous activator of SIRT6 and facilitates chromatin localization of SIRT6 upon DNA damage. Lamin A promotes SIRT6-dependent DNA-PKcs (DNA-PK catalytic subunit) recruitment to chromatin, CtIP deacetylation, and PARP1 mono-ADP ribosylation in response to DNA damage. The presence of progerin jeopardizes SIRT6 activation and compromises SIRT6-mediated molecular events in response to DNA damage. These data reveal a critical role for lamin A in regulating SIRT6 activities, suggesting that defects in SIRT6 functions contribute to impaired DNA repair and accelerated aging in HGPS.http://www.sciencedirect.com/science/article/pii/S2211124715011456 |
| spellingShingle | Shrestha Ghosh Baohua Liu Yi Wang Quan Hao Zhongjun Zhou Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair Cell Reports |
| title | Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair |
| title_full | Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair |
| title_fullStr | Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair |
| title_full_unstemmed | Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair |
| title_short | Lamin A Is an Endogenous SIRT6 Activator and Promotes SIRT6-Mediated DNA Repair |
| title_sort | lamin a is an endogenous sirt6 activator and promotes sirt6 mediated dna repair |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715011456 |
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