The molecular basis of chromatin dynamics during nucleotide excision repairThis paper is one of a selection of papers published in this Special Issue, entitled 29th Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.

The assembly of DNA into chromatin in eukaryotic cells affects all DNA-related cellular activities, such as replication, transcription, recombination, and repair. Rearrangement of chromatin structure during nucleotide excision repair (NER) was discovered more than 2 decades ago. However, the molecular basis of chromatin dynamics during NER remains undefined. Pioneering studies in the field of gene transcription have shown that ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes play a critical role in chromatin dynamics during transcription. Similarly, recent studies have demonstrated that the SWI/SNF chromatin-remodeling complex facilitates NER both in vitro and in vivo. Additionally, histone acetylation has also been linked to the NER of ultraviolet light damage. In this article, we will discuss the role of these identified chromatin-modifying activities in NER.

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PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1

The Journal of Cell Biology ◽

10.1083/jcb.201112132 ◽

2012 ◽

Vol 199 (2) ◽

pp. 235-249 ◽

Cited By ~ 129

Author(s):

Alex Pines ◽

Mischa G. Vrouwe ◽

Jurgen A. Marteijn ◽

Dimitris Typas ◽

Martijn S. Luijsterburg ◽

...

Keyword(s):

Nucleotide Excision Repair ◽

Chromatin Remodeling ◽

Excision Repair ◽

Dna Lesions ◽

Subsequent Removal ◽

Wd40 Repeat ◽

Nucleotide Excision ◽

Efficient Recognition

The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1.

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Nucleotide Excision Repair in Human Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m113.482257 ◽

2013 ◽

Vol 288 (29) ◽

pp. 20918-20926 ◽

Cited By ~ 52

Author(s):

Jinchuan Hu ◽

Jun-Hyuk Choi ◽

Shobhan Gaddameedhi ◽

Michael G. Kemp ◽

Joyce T. Reardon ◽

...

Keyword(s):

Nucleotide Excision Repair ◽

Genomic Dna ◽

Excision Repair ◽

Human Cells ◽

Naked Dna ◽

Nucleotide Excision ◽

Uv Photoproducts ◽

Mutant Cells

Nucleotide excision repair is the sole mechanism for removing the major UV photoproducts from genomic DNA in human cells. In vitro with human cell-free extract or purified excision repair factors, the damage is removed from naked DNA or nucleosomes in the form of 24- to 32-nucleotide-long oligomers (nominal 30-mer) by dual incisions. Whether the DNA damage is removed from chromatin in vivo in a similar manner and what the fate of the excised oligomer was has not been known previously. Here, we demonstrate that dual incisions occur in vivo identical to the in vitro reaction. Further, we show that transcription-coupled repair, which operates in the absence of the XPC protein, also generates the nominal 30-mer in UV-irradiated XP-C mutant cells. Finally, we report that the excised 30-mer is released from the chromatin in complex with the repair factors TFIIH and XPG. Taken together, our results show the congruence of in vivo and in vitro data on nucleotide excision repair in humans.

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Hairless is a nuclear receptor corepressor essential for skin function

Nuclear Receptor Signaling ◽

10.1621/nrs.07010 ◽

2009 ◽

Vol 7 (1) ◽

pp. nrs.07010 ◽

Cited By ~ 19

Author(s):

Catherine C. Thompson

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Nuclear Receptors ◽

Chromatin Remodeling ◽

Transcriptional Repression ◽

Critical Role ◽

Epithelial Stem Cells ◽

Skin Function

The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling.

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Structure of theArabidopsisTOPLESS corepressor provides insight into the evolution of transcriptional repression

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1703054114 ◽

2017 ◽

Vol 114 (30) ◽

pp. 8107-8112 ◽

Cited By ~ 23

Author(s):

Raquel Martin-Arevalillo ◽

Max H. Nanao ◽

Antoine Larrieu ◽

Thomas Vinos-Poyo ◽

David Mast ◽

...

Keyword(s):

Chromatin Remodeling ◽

Transcriptional Repression ◽

Site Directed Mutagenesis ◽

Crystallographic Structure ◽

Hormone Signaling ◽

Chromatin Remodeling Complexes ◽

Insight Into ◽

Similar Domain

Transcriptional repression involves a class of proteins called corepressors that link transcription factors to chromatin remodeling complexes. In plants such asArabidopsis thaliana, the most prominent corepressor is TOPLESS (TPL), which plays a key role in hormone signaling and development. Here we present the crystallographic structure of theArabidopsisTPL N-terminal region comprising the LisH and CTLH (C-terminal to LisH) domains and a newly identified third region, which corresponds to a CRA domain. Comparing the structure of TPL with the mammalian TBL1, which shares a similar domain structure and performs a parallel corepressor function, revealed that the plant TPLs have evolved a new tetramerization interface and unique and highly conserved surface for interaction with repressors. Using site-directed mutagenesis, we validated those surfaces in vitro and in vivo and showed that TPL tetramerization and repressor binding are interdependent. Our results illustrate how evolution used a common set of protein domains to create a diversity of corepressors, achieving similar properties with different molecular solutions.

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Phloroglucinol enhances the repair of UVB radiation-induced DNA damage via promotion of the nucleotide excision repair system in vitro and in vivo

DNA Repair ◽

10.1016/j.dnarep.2015.02.019 ◽

2015 ◽

Vol 28 ◽

pp. 131-138 ◽

Cited By ~ 9

Author(s):

Mei Jing Piao ◽

Mee Jung Ahn ◽

Kyoung Ah Kang ◽

Ki Cheon Kim ◽

Ji Won Cha ◽

...

Keyword(s):

Dna Damage ◽

Nucleotide Excision Repair ◽

Excision Repair ◽

Repair System ◽

Uvb Radiation ◽

Nucleotide Excision ◽

Radiation Induced ◽

Nucleotide Excision Repair System

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Neutrophils inhibit pulmonary nucleotide excision repair: Evidence from in vitro and in vivo studies

Chemico-Biological Interactions ◽

10.1016/j.cbi.2007.06.009 ◽

2007 ◽

Vol 169 (2) ◽

pp. 134

Author(s):

N. Güngör ◽

R.W.L. Godschalk ◽

D. Pachen ◽

A. Haegens ◽

F.J. Van Schooten ◽

...

Keyword(s):

Nucleotide Excision Repair ◽

Excision Repair ◽

In Vivo Studies ◽

Nucleotide Excision

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UvrD Participation in Nucleotide Excision Repair Is Required for the Recovery of DNA Synthesis following UV-Induced Damage inEscherichia coli

Journal of Nucleic Acids ◽

10.1155/2012/271453 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Kelley N. Newton ◽

Charmain T. Courcelle ◽

Justin Courcelle

Keyword(s):

Dna Damage ◽

Dna Synthesis ◽

Nucleotide Excision Repair ◽

Excision Repair ◽

Dna Helicase ◽

Replication Forks ◽

Nucleotide Excision ◽

Fork Regression

UvrD is a DNA helicase that participates in nucleotide excision repair and several replication-associated processes, including methyl-directed mismatch repair and recombination. UvrD is capable of displacing oligonucleotides from synthetic forked DNA structuresin vitroand is essential for viability in the absence of Rep, a helicase associated with processing replication forks. These observations have led others to propose that UvrD may promote fork regression and facilitate resetting of the replication fork following arrest. However, the molecular activity of UvrD at replication forksin vivohas not been directly examined. In this study, we characterized the role UvrD has in processing and restoring replication forks following arrest by UV-induced DNA damage. We show that UvrD is required for DNA synthesis to recover. However, in the absence of UvrD, the displacement and partial degradation of the nascent DNA at the arrested fork occur normally. In addition, damage-induced replication intermediates persist and accumulate inuvrDmutants in a manner that is similar to that observed in other nucleotide excision repair mutants. These data indicate that, following arrest by DNA damage, UvrD is not required to catalyze fork regressionin vivoand suggest that the failure ofuvrDmutants to restore DNA synthesis following UV-induced arrest relates to its role in nucleotide excision repair.

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UV radiation-induced SUMOylation of DDB2 regulates nucleotide excision repair

Carcinogenesis ◽

10.1093/carcin/bgx076 ◽

2017 ◽

Vol 38 (10) ◽

pp. 976-985 ◽

Cited By ~ 7

Author(s):

Chunhua Han ◽

Ran Zhao ◽

John Kroger ◽

Jinshan He ◽

Gulzar Wani ◽

...

Keyword(s):

Dna Damage ◽

Nucleotide Excision Repair ◽

Uv Radiation ◽

Uv Irradiation ◽

Excision Repair ◽

26S Proteasome ◽

Cell Extracts ◽

Nucleotide Excision

Abstract Subunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications. We, for the first time, show that the appearance of UVR-induced DDB2 modifications depend on the binding of DDB2 to the damaged chromatin and the participation of functionally active 26S proteasome. The in vitro and in vivo analysis revealed that SUMO-1 conjugations comprise a significant portion of these UVR-induced DDB2 modifications. Mapping of SUMO-modified sites demonstrated that UVR-induced SUMOylation occurs on Lys-309 residue of DDB2 protein. Mutation of Lys-309 to Arg-309 diminished the DDB2 SUMOylation observable both in vitro and in vivo. Moreover, K309R mutated DDB2 lost its function of recruiting XPC to the DNA damage sites, as well as the ability to repair cyclobutane pyrimidine dimers following cellular UV irradiation. Taken together, our results indicate that DDB2 is modified by SUMOylation upon UV irradiation, and this post-translational modification plays an important role in the initial recognition and processing of UVR-induced DNA damage occurring within the context of chromatin.

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Connection between histone H2A variants and chromatin remodeling complexesThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.

Biochemistry and Cell Biology ◽

10.1139/o08-140 ◽

2009 ◽

Vol 87 (1) ◽

pp. 35-50 ◽

Cited By ~ 47

Author(s):

Mohammed Altaf ◽

Andréanne Auger ◽

Marcela Covic ◽

Jacques Côté

Keyword(s):

Chromatin Remodeling ◽

Chromatin Structure ◽

Cellular Response ◽

Peer Review Process ◽

Histone Variants ◽

Histone H2a ◽

Chromatin Dynamics ◽

Recent Developments ◽

Chromatin Remodeling Complexes ◽

And Function

The organization of the eukaryotic genome into chromatin makes it inaccessible to the factors required for gene transcription and DNA replication, recombination, and repair. In addition to histone-modifying enzymes and ATP-dependent chromatin remodeling complexes, which play key roles in regulating many nuclear processes by altering the chromatin structure, cells have developed a mechanism of modulating chromatin structure by incorporating histone variants. These variants are incorporated into specific regions of the genome throughout the cell cycle. H2A.Z, which is an evolutionarily conserved H2A variant, performs several seemingly unrelated and even contrary functions. Another H2A variant, H2A.X, plays a very important role in the cellular response to DNA damage. This review summarizes the recent developments in our understanding of the role of H2A.Z and H2A.X in the regulation of chromatin structure and function, focusing on their functional links with chromatin modifying and remodeling complexes.

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