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ATP-dependent chromatin remodeling in the DNA-damage response.

Lans H, Marteijn JA, Vermeulen W - Epigenetics Chromatin (2012)

Bottom Line: Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response.In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response.This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Medical Genetics Center, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. w.vermeulen@erasmusmc.nl.

ABSTRACT
The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.

No MeSH data available.


Related in: MedlinePlus

Mammalian nucleotide excision repair (NER)-associated chromatin remodeling. Both the SWI/SNF and the INO80 ATP-dependent chromatin-remodeling complexes are recruited to sites of UV-induced DNA damage, and are implicated in mammalian global genome NER (GG-NER). SWI/SNF may interact with the damage-detection complexes XPC/RAD23 and UV-DDB, and stimulate recruitment of XPC to the damage. Recruitment of SWI/SNF is also stimulated by XPC. In addition, mammalian INO80 interacts with UV-DDB, and stimulates recruitment of XPC. Together, SWI/SNF and INO80 are thought to regulate accessibility of DNA by sliding or eviction of nucleosomes at the damaged site. Red dotted arrows depict chromatin recruitment and protein-protein interactions. See main text for details and references.
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Figure 2: Mammalian nucleotide excision repair (NER)-associated chromatin remodeling. Both the SWI/SNF and the INO80 ATP-dependent chromatin-remodeling complexes are recruited to sites of UV-induced DNA damage, and are implicated in mammalian global genome NER (GG-NER). SWI/SNF may interact with the damage-detection complexes XPC/RAD23 and UV-DDB, and stimulate recruitment of XPC to the damage. Recruitment of SWI/SNF is also stimulated by XPC. In addition, mammalian INO80 interacts with UV-DDB, and stimulates recruitment of XPC. Together, SWI/SNF and INO80 are thought to regulate accessibility of DNA by sliding or eviction of nucleosomes at the damaged site. Red dotted arrows depict chromatin recruitment and protein-protein interactions. See main text for details and references.

Mentions: Besides BRG1, the mammalian SWI/SNF subunit SNF5/SMARCB1 also interacts with XPC [61]. Inactivation of SNF5 causes UV hypersensitivity and inefficient CPD repair [60,62], although this has been challenged by a study in which no effect of SNF5 depletion on UV sensitivity was found [63]. These differences may be due to the use of different assays and cells. In a genetic screen, our laboratory identified different subunits of SWI/SNF complexes, including orthologs of mammalian BRG1 and BRM/SMARCA2, SNF5, PBRM1 and BAF155/SMARCC1, which are essential for optimal UV survival of somatic cells in Caenorhabditis elegans [64]. Intriguingly, BRG1/BRM, but none of the other subunits, is also important to the UV response of germ cells, suggesting that the involvement of individual SWI/SNF subunits may differ between cell types. Importantly, UV hypersensitivity resulting from BRG1 inactivation depends on the presence of the checkpoint protein TP53 [58], extending the complexity of the involvement of BRG1 in UV-induced DDR. How exactly SWI/SNF remodelers impinge on NER is as yet unknown, but the available data support a regulatory role in the damage-detection step of NER (Figure 2).


ATP-dependent chromatin remodeling in the DNA-damage response.

Lans H, Marteijn JA, Vermeulen W - Epigenetics Chromatin (2012)

Mammalian nucleotide excision repair (NER)-associated chromatin remodeling. Both the SWI/SNF and the INO80 ATP-dependent chromatin-remodeling complexes are recruited to sites of UV-induced DNA damage, and are implicated in mammalian global genome NER (GG-NER). SWI/SNF may interact with the damage-detection complexes XPC/RAD23 and UV-DDB, and stimulate recruitment of XPC to the damage. Recruitment of SWI/SNF is also stimulated by XPC. In addition, mammalian INO80 interacts with UV-DDB, and stimulates recruitment of XPC. Together, SWI/SNF and INO80 are thought to regulate accessibility of DNA by sliding or eviction of nucleosomes at the damaged site. Red dotted arrows depict chromatin recruitment and protein-protein interactions. See main text for details and references.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275488&req=5

Figure 2: Mammalian nucleotide excision repair (NER)-associated chromatin remodeling. Both the SWI/SNF and the INO80 ATP-dependent chromatin-remodeling complexes are recruited to sites of UV-induced DNA damage, and are implicated in mammalian global genome NER (GG-NER). SWI/SNF may interact with the damage-detection complexes XPC/RAD23 and UV-DDB, and stimulate recruitment of XPC to the damage. Recruitment of SWI/SNF is also stimulated by XPC. In addition, mammalian INO80 interacts with UV-DDB, and stimulates recruitment of XPC. Together, SWI/SNF and INO80 are thought to regulate accessibility of DNA by sliding or eviction of nucleosomes at the damaged site. Red dotted arrows depict chromatin recruitment and protein-protein interactions. See main text for details and references.
Mentions: Besides BRG1, the mammalian SWI/SNF subunit SNF5/SMARCB1 also interacts with XPC [61]. Inactivation of SNF5 causes UV hypersensitivity and inefficient CPD repair [60,62], although this has been challenged by a study in which no effect of SNF5 depletion on UV sensitivity was found [63]. These differences may be due to the use of different assays and cells. In a genetic screen, our laboratory identified different subunits of SWI/SNF complexes, including orthologs of mammalian BRG1 and BRM/SMARCA2, SNF5, PBRM1 and BAF155/SMARCC1, which are essential for optimal UV survival of somatic cells in Caenorhabditis elegans [64]. Intriguingly, BRG1/BRM, but none of the other subunits, is also important to the UV response of germ cells, suggesting that the involvement of individual SWI/SNF subunits may differ between cell types. Importantly, UV hypersensitivity resulting from BRG1 inactivation depends on the presence of the checkpoint protein TP53 [58], extending the complexity of the involvement of BRG1 in UV-induced DDR. How exactly SWI/SNF remodelers impinge on NER is as yet unknown, but the available data support a regulatory role in the damage-detection step of NER (Figure 2).

Bottom Line: Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response.In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response.This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Medical Genetics Center, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. w.vermeulen@erasmusmc.nl.

ABSTRACT
The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.

No MeSH data available.


Related in: MedlinePlus