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The emerging roles of ATP-dependent chromatin remodeling enzymes in nucleotide excision repair.

Czaja W, Mao P, Smerdon MJ - Int J Mol Sci (2012)

Bottom Line: ATP-dependent chromatin remodelers (ACRs) are the master regulators of chromatin structure and dynamics.Conserved from yeast to humans, ACRs utilize the energy of ATP to reorganize packing of chromatin and control DNA accessibility by sliding, ejecting or restructuring nucleosomes.We discuss current understanding of ATP-dependent chromatin remodeling by various subfamilies of remodelers and regulation of the NER pathway in vivo.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, WA, USA; E-Mails: wiolettapyrzak@vetmed.wsu.edu (W.C.); pengmao@vetmed.wsu.edu (P.M.).

ABSTRACT
DNA repair in eukaryotic cells takes place in the context of chromatin, where DNA, including damaged DNA, is tightly packed into nucleosomes and higher order chromatin structures. Chromatin intrinsically restricts accessibility of DNA repair proteins to the damaged DNA and impacts upon the overall rate of DNA repair. Chromatin is highly responsive to DNA damage and undergoes specific remodeling to facilitate DNA repair. How damaged DNA is accessed, repaired and restored to the original chromatin state, and how chromatin remodeling coordinates these processes in vivo, remains largely unknown. ATP-dependent chromatin remodelers (ACRs) are the master regulators of chromatin structure and dynamics. Conserved from yeast to humans, ACRs utilize the energy of ATP to reorganize packing of chromatin and control DNA accessibility by sliding, ejecting or restructuring nucleosomes. Several studies have demonstrated that ATP-dependent remodeling activity of ACRs plays important roles in coordination of spatio-temporal steps of different DNA repair pathways in chromatin. This review focuses on the role of ACRs in regulation of various aspects of nucleotide excision repair (NER) in the context of chromatin. We discuss current understanding of ATP-dependent chromatin remodeling by various subfamilies of remodelers and regulation of the NER pathway in vivo.

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Related in: MedlinePlus

Inactivation of switching defective/Sucrose nonfermenting (SWI/SNF) affects the rate of global genome repair (GGR) at the silent HML locus in yeast cells. (a) Schematic diagram of the HML locus, including a1 and a2 mating-type genes and essential (E) and important (I) cis-acting silencer sequences that maintain transcription silencing; (b) Representative gel showing CPD removal. Yeast cells were UV-irradiated and incubated for times indicated. DNA purified from cells was assayed using the CPD-specific T4 endonuclease V (T4 endo V); (c) Time course for CPD removal. Data represent means ± SD from three independent experiments. snf6 (pSnf6) strain expresses Snf6 from a plasmid; (d) Schematic diagram of the nucleosome-loaded HML locus. Ovals represent nucleosomes whose positions have been mapped at nucleotide resolution20; (e) Accessibility of the EcoRV site at the HML locus in chromatin of isolated nuclei after UV irradiation; (f) Quantitative data showing the percentage of DNA accessible to EcoRV.
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f1-ijms-13-11954: Inactivation of switching defective/Sucrose nonfermenting (SWI/SNF) affects the rate of global genome repair (GGR) at the silent HML locus in yeast cells. (a) Schematic diagram of the HML locus, including a1 and a2 mating-type genes and essential (E) and important (I) cis-acting silencer sequences that maintain transcription silencing; (b) Representative gel showing CPD removal. Yeast cells were UV-irradiated and incubated for times indicated. DNA purified from cells was assayed using the CPD-specific T4 endonuclease V (T4 endo V); (c) Time course for CPD removal. Data represent means ± SD from three independent experiments. snf6 (pSnf6) strain expresses Snf6 from a plasmid; (d) Schematic diagram of the nucleosome-loaded HML locus. Ovals represent nucleosomes whose positions have been mapped at nucleotide resolution20; (e) Accessibility of the EcoRV site at the HML locus in chromatin of isolated nuclei after UV irradiation; (f) Quantitative data showing the percentage of DNA accessible to EcoRV.

Mentions: Gong et al. provided direct evidence in vivo linking the SWI/SNF complex with NER in intact yeast cells [59]. A major finding of this report was demonstration of direct interactions between the subunit of SWI/SNF, SNF6, and the lesion recognition heterodimer Rad23-Rad4 (the ortholog of human XPC-hHR23B). The SWI/SNF interaction with RAD23-Rad4 was enhanced in a UV-dependent manner, suggesting that the remodeler might be specifically recruited to sites of damage by NER lesion recognition proteins. Furthermore, this study demonstrated a specific role of SWI/SNF during GG-NER. That is, the SWI/SNF complex is required for efficient removal of CPDs by GG-NER at the silent (nucleosome-loaded) HML locus (Figure 1a–c). Additionally, it was found that chromatin accessibility at HML was significantly decreased in SWI/SNF deficient yeast cells (Figure 1d–f). Collectively, these data suggest that SWI/SNF contributes to UV-induced chromatin remodeling, in at least certain regions of chromatin, facilitating DNA accessibility and enhancing NER in vivo.


The emerging roles of ATP-dependent chromatin remodeling enzymes in nucleotide excision repair.

Czaja W, Mao P, Smerdon MJ - Int J Mol Sci (2012)

Inactivation of switching defective/Sucrose nonfermenting (SWI/SNF) affects the rate of global genome repair (GGR) at the silent HML locus in yeast cells. (a) Schematic diagram of the HML locus, including a1 and a2 mating-type genes and essential (E) and important (I) cis-acting silencer sequences that maintain transcription silencing; (b) Representative gel showing CPD removal. Yeast cells were UV-irradiated and incubated for times indicated. DNA purified from cells was assayed using the CPD-specific T4 endonuclease V (T4 endo V); (c) Time course for CPD removal. Data represent means ± SD from three independent experiments. snf6 (pSnf6) strain expresses Snf6 from a plasmid; (d) Schematic diagram of the nucleosome-loaded HML locus. Ovals represent nucleosomes whose positions have been mapped at nucleotide resolution20; (e) Accessibility of the EcoRV site at the HML locus in chromatin of isolated nuclei after UV irradiation; (f) Quantitative data showing the percentage of DNA accessible to EcoRV.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472786&req=5

f1-ijms-13-11954: Inactivation of switching defective/Sucrose nonfermenting (SWI/SNF) affects the rate of global genome repair (GGR) at the silent HML locus in yeast cells. (a) Schematic diagram of the HML locus, including a1 and a2 mating-type genes and essential (E) and important (I) cis-acting silencer sequences that maintain transcription silencing; (b) Representative gel showing CPD removal. Yeast cells were UV-irradiated and incubated for times indicated. DNA purified from cells was assayed using the CPD-specific T4 endonuclease V (T4 endo V); (c) Time course for CPD removal. Data represent means ± SD from three independent experiments. snf6 (pSnf6) strain expresses Snf6 from a plasmid; (d) Schematic diagram of the nucleosome-loaded HML locus. Ovals represent nucleosomes whose positions have been mapped at nucleotide resolution20; (e) Accessibility of the EcoRV site at the HML locus in chromatin of isolated nuclei after UV irradiation; (f) Quantitative data showing the percentage of DNA accessible to EcoRV.
Mentions: Gong et al. provided direct evidence in vivo linking the SWI/SNF complex with NER in intact yeast cells [59]. A major finding of this report was demonstration of direct interactions between the subunit of SWI/SNF, SNF6, and the lesion recognition heterodimer Rad23-Rad4 (the ortholog of human XPC-hHR23B). The SWI/SNF interaction with RAD23-Rad4 was enhanced in a UV-dependent manner, suggesting that the remodeler might be specifically recruited to sites of damage by NER lesion recognition proteins. Furthermore, this study demonstrated a specific role of SWI/SNF during GG-NER. That is, the SWI/SNF complex is required for efficient removal of CPDs by GG-NER at the silent (nucleosome-loaded) HML locus (Figure 1a–c). Additionally, it was found that chromatin accessibility at HML was significantly decreased in SWI/SNF deficient yeast cells (Figure 1d–f). Collectively, these data suggest that SWI/SNF contributes to UV-induced chromatin remodeling, in at least certain regions of chromatin, facilitating DNA accessibility and enhancing NER in vivo.

Bottom Line: ATP-dependent chromatin remodelers (ACRs) are the master regulators of chromatin structure and dynamics.Conserved from yeast to humans, ACRs utilize the energy of ATP to reorganize packing of chromatin and control DNA accessibility by sliding, ejecting or restructuring nucleosomes.We discuss current understanding of ATP-dependent chromatin remodeling by various subfamilies of remodelers and regulation of the NER pathway in vivo.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, WA, USA; E-Mails: wiolettapyrzak@vetmed.wsu.edu (W.C.); pengmao@vetmed.wsu.edu (P.M.).

ABSTRACT
DNA repair in eukaryotic cells takes place in the context of chromatin, where DNA, including damaged DNA, is tightly packed into nucleosomes and higher order chromatin structures. Chromatin intrinsically restricts accessibility of DNA repair proteins to the damaged DNA and impacts upon the overall rate of DNA repair. Chromatin is highly responsive to DNA damage and undergoes specific remodeling to facilitate DNA repair. How damaged DNA is accessed, repaired and restored to the original chromatin state, and how chromatin remodeling coordinates these processes in vivo, remains largely unknown. ATP-dependent chromatin remodelers (ACRs) are the master regulators of chromatin structure and dynamics. Conserved from yeast to humans, ACRs utilize the energy of ATP to reorganize packing of chromatin and control DNA accessibility by sliding, ejecting or restructuring nucleosomes. Several studies have demonstrated that ATP-dependent remodeling activity of ACRs plays important roles in coordination of spatio-temporal steps of different DNA repair pathways in chromatin. This review focuses on the role of ACRs in regulation of various aspects of nucleotide excision repair (NER) in the context of chromatin. We discuss current understanding of ATP-dependent chromatin remodeling by various subfamilies of remodelers and regulation of the NER pathway in vivo.

Show MeSH
Related in: MedlinePlus