Limits...
Chromatin dynamics during nucleotide excision repair: histones on the move.

Adam S, Polo SE - Int J Mol Sci (2012)

Bottom Line: Several decades of analysis combining in vitro and in vivo studies in various model organisms ranging from yeast to human have markedly increased our understanding of the mechanisms underlying chromatin disorganization upon damage detection and re-assembly after repair.We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, raising new issues about the maintenance of chromatin integrity.In particular, we discuss how NER factors and central players in chromatin dynamics such as histone modifiers, nucleosome remodeling factors, and histone chaperones function to mobilize histones during repair.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chromatin Dynamics, Curie Institute Research Centre, 75248 Paris Cedex 5, France; E-Mail: salome.adam@curie.fr ; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 218, 75248 Paris Cedex 5, France.

ABSTRACT
It has been a long-standing question how DNA damage repair proceeds in a nuclear environment where DNA is packaged into chromatin. Several decades of analysis combining in vitro and in vivo studies in various model organisms ranging from yeast to human have markedly increased our understanding of the mechanisms underlying chromatin disorganization upon damage detection and re-assembly after repair. Here, we review the methods that have been developed over the years to delineate chromatin alterations in response to DNA damage by focusing on the well-characterized Nucleotide Excision Repair (NER) pathway. We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, raising new issues about the maintenance of chromatin integrity. In particular, we discuss how NER factors and central players in chromatin dynamics such as histone modifiers, nucleosome remodeling factors, and histone chaperones function to mobilize histones during repair.

Show MeSH

Related in: MedlinePlus

Methods for inducing DNA damage repaired by the Nucleotide Excision Repair (NER) pathway. When not chemically synthesized, DNA lesions (i.e., pyrimidine dimers and bulky DNA adducts, red triangles) are generally induced by exposure to UV light and/or cross-linking agents (purple). Genotoxic treatment is applied on DNA templates (in vitro) or on cultured human cells (in vivo). Damaged DNA templates are further immobilized onto magnetic beads [19] or used to reconstitute nucleosome particles by salt dialysis [20,21]. Global cell irradiation with a UVC lamp generates DNA damage throughout the nucleus. Localized DNA damage is induced by irradiating cells with a UVC lamp through a micropore filter [22–24] or by focusing a UVC laser to specific sub-nuclear regions [25].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3472782&req=5

f1-ijms-13-11895: Methods for inducing DNA damage repaired by the Nucleotide Excision Repair (NER) pathway. When not chemically synthesized, DNA lesions (i.e., pyrimidine dimers and bulky DNA adducts, red triangles) are generally induced by exposure to UV light and/or cross-linking agents (purple). Genotoxic treatment is applied on DNA templates (in vitro) or on cultured human cells (in vivo). Damaged DNA templates are further immobilized onto magnetic beads [19] or used to reconstitute nucleosome particles by salt dialysis [20,21]. Global cell irradiation with a UVC lamp generates DNA damage throughout the nucleus. Localized DNA damage is induced by irradiating cells with a UVC lamp through a micropore filter [22–24] or by focusing a UVC laser to specific sub-nuclear regions [25].

Mentions: Over the past decades, a series of methods have been developed both in vitro and in vivo to assess histone and nucleosome dynamics coupled to NER (Figures 1–3), considerably increasing our understanding of chromatin rearrangements during the NER process.


Chromatin dynamics during nucleotide excision repair: histones on the move.

Adam S, Polo SE - Int J Mol Sci (2012)

Methods for inducing DNA damage repaired by the Nucleotide Excision Repair (NER) pathway. When not chemically synthesized, DNA lesions (i.e., pyrimidine dimers and bulky DNA adducts, red triangles) are generally induced by exposure to UV light and/or cross-linking agents (purple). Genotoxic treatment is applied on DNA templates (in vitro) or on cultured human cells (in vivo). Damaged DNA templates are further immobilized onto magnetic beads [19] or used to reconstitute nucleosome particles by salt dialysis [20,21]. Global cell irradiation with a UVC lamp generates DNA damage throughout the nucleus. Localized DNA damage is induced by irradiating cells with a UVC lamp through a micropore filter [22–24] or by focusing a UVC laser to specific sub-nuclear regions [25].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472782&req=5

f1-ijms-13-11895: Methods for inducing DNA damage repaired by the Nucleotide Excision Repair (NER) pathway. When not chemically synthesized, DNA lesions (i.e., pyrimidine dimers and bulky DNA adducts, red triangles) are generally induced by exposure to UV light and/or cross-linking agents (purple). Genotoxic treatment is applied on DNA templates (in vitro) or on cultured human cells (in vivo). Damaged DNA templates are further immobilized onto magnetic beads [19] or used to reconstitute nucleosome particles by salt dialysis [20,21]. Global cell irradiation with a UVC lamp generates DNA damage throughout the nucleus. Localized DNA damage is induced by irradiating cells with a UVC lamp through a micropore filter [22–24] or by focusing a UVC laser to specific sub-nuclear regions [25].
Mentions: Over the past decades, a series of methods have been developed both in vitro and in vivo to assess histone and nucleosome dynamics coupled to NER (Figures 1–3), considerably increasing our understanding of chromatin rearrangements during the NER process.

Bottom Line: Several decades of analysis combining in vitro and in vivo studies in various model organisms ranging from yeast to human have markedly increased our understanding of the mechanisms underlying chromatin disorganization upon damage detection and re-assembly after repair.We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, raising new issues about the maintenance of chromatin integrity.In particular, we discuss how NER factors and central players in chromatin dynamics such as histone modifiers, nucleosome remodeling factors, and histone chaperones function to mobilize histones during repair.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chromatin Dynamics, Curie Institute Research Centre, 75248 Paris Cedex 5, France; E-Mail: salome.adam@curie.fr ; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 218, 75248 Paris Cedex 5, France.

ABSTRACT
It has been a long-standing question how DNA damage repair proceeds in a nuclear environment where DNA is packaged into chromatin. Several decades of analysis combining in vitro and in vivo studies in various model organisms ranging from yeast to human have markedly increased our understanding of the mechanisms underlying chromatin disorganization upon damage detection and re-assembly after repair. Here, we review the methods that have been developed over the years to delineate chromatin alterations in response to DNA damage by focusing on the well-characterized Nucleotide Excision Repair (NER) pathway. We also highlight how these methods have provided key mechanistic insight into histone dynamics coupled to repair in mammals, raising new issues about the maintenance of chromatin integrity. In particular, we discuss how NER factors and central players in chromatin dynamics such as histone modifiers, nucleosome remodeling factors, and histone chaperones function to mobilize histones during repair.

Show MeSH
Related in: MedlinePlus