Biomolecules

1081 KiB

Open AccessArticle

Morphological and Functional Analysis of Hepatocyte Spheroids Generated on Poly-HEMA-Treated Surfaces under the Influence of Fetal Calf Serum and Nonparenchymal Cells

by Ali Acikgöz, Shibashish Giri, Man-Gi Cho and Augustinus Bader

Biomolecules 2013, 3(1), 242-269; https://doi.org/10.3390/biom3010242 - 7 Mar 2013

Cited by 30 | Viewed by 9972

Abstract

Poly (2-hydroxyethyl methacrylate) (HEMA) has been used as a clinical material, in the form of a soft hydrogel, for various surgical procedures, including endovascular surgery of liver. It is a clear liquid compound and, as a soft, flexible, water-absorbing material, has been used [...] Read more.

Poly (2-hydroxyethyl methacrylate) (HEMA) has been used as a clinical material, in the form of a soft hydrogel, for various surgical procedures, including endovascular surgery of liver. It is a clear liquid compound and, as a soft, flexible, water-absorbing material, has been used to make soft contact lenses from small, concave, spinning molds. Primary rat hepatocyte spheroids were created on a poly-HEMA-coated surface with the intention of inducing hepatic tissue formation and improving liver functions. We investigated spheroid formation of primary adult rat hepatocyte cells and characterized hepatic-specific functions under the special influence of fetal calf serum (FCS) and nonparencymal cells (NPC) up to six days in different culture systems (e.g., hepatocytes + FCS, hepatocytes – FCS, NPC + FCS, NPC – FCS, co-culture + FCS, co-culture – FCS) in both the spheroid model and sandwich model. Immunohistologically, we detected gap junctions, Ito cell/Kupffer cells, sinusoidal endothelial cells and an extracellular matrix in the spheroid model. FCS has no positive effect in the sandwich model, but has a negative effect in the spheroid model on albumin production, and no influence in urea production in either model. We found more cell viability in smaller diameter spheroids than larger ones by using the apoptosis test. Furthermore, there is no positive influence of the serum or NPC on spheroid formation, suggesting that it may only depend on the physical condition of the culture system. Since the sandwich culture has been considered a “gold standard” in vitro culture model, the hepatocyte spheroids generated on the poly-HEMA-coated surface were compared with those in the sandwich model. Major liver-specific functions, such as albumin secretion and urea synthesis, were evaluated in both the spheroid and sandwich model. The synthesis performance in the spheroid compared to the sandwich culture increases approximately by a factor of 1.5. Disintegration of plasma membranes in both models was measured by lactate dehydrogenase (LDH) release in both models. Additionally, diazepam was used as a substrate in drug metabolism studies to characterize the differences in the biotransformation potential with metabolite profiles in both models. It showed that the diazepam metabolism activities in the spheroid model is about 10-fold lower than the sandwich model. The poly-HEMA-based hepatocyte spheroid is a promising new platform towards hepatic tissue engineering leading to in vitro hepatic tissue formation. Full article

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365 KiB

Open AccessReview

Panning for Long Noncoding RNAs

by Shanshan Zhu, Xiao-Ou Zhang and Li Yang

Biomolecules 2013, 3(1), 226-241; https://doi.org/10.3390/biom3010226 - 28 Feb 2013

Cited by 12 | Viewed by 8595

Abstract

The recent advent of high-throughput approaches has revealed widespread transcription of the human genome, leading to a new appreciation of transcription regulation, especially from noncoding regions. Distinct from most coding and small noncoding RNAs, long noncoding RNAs (lncRNAs) are generally expressed at low [...] Read more.

The recent advent of high-throughput approaches has revealed widespread transcription of the human genome, leading to a new appreciation of transcription regulation, especially from noncoding regions. Distinct from most coding and small noncoding RNAs, long noncoding RNAs (lncRNAs) are generally expressed at low levels, are less conserved and lack protein-coding capacity. These intrinsic features of lncRNAs have not only hampered their full annotation in the past several years, but have also generated controversy concerning whether many or most of these lncRNAs are simply the result of transcriptional noise. Here, we assess these intrinsic features that have challenged lncRNA discovery and further summarize recent progress in lncRNA discovery with integrated methodologies, from which new lessons and insights can be derived to achieve better characterization of lncRNA expression regulation. Full annotation of lncRNA repertoires and the implications of such annotation will provide a fundamental basis for comprehensive understanding of pervasive functions of lncRNAs in biological regulation. Full article

(This article belongs to the Special Issue Non-coding RNA)

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691 KiB

Open AccessReview

Recent Advances in Cellular Glycomic Analyses

by Jun-ichi Furukawa, Naoki Fujitani and Yasuro Shinohara

Biomolecules 2013, 3(1), 198-225; https://doi.org/10.3390/biom3010198 - 21 Feb 2013

Cited by 26 | Viewed by 8651

Abstract

A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated [...] Read more.

A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed. Full article

(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)

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701 KiB

Open AccessArticle

Multi-Color Spectral Transcript Analysis (SPECTRA) for Phenotypic Characterization of Tumor Cells

by Joanne H. Hsu, Jingly F. Weier, Heinz-Ulrich G. Weier and Yuko Ito

Biomolecules 2013, 3(1), 180-197; https://doi.org/10.3390/biom3010180 - 11 Feb 2013

Viewed by 6658

Abstract

Many human tumors show significant changes in their signal transduction pathways and, thus, the way the cells interact with their environment. Often caused by chromosomal rearrangements, including gene amplifications, translocations or deletions, the altered levels of gene expression may provide a tumor-specific signature [...] Read more.

Many human tumors show significant changes in their signal transduction pathways and, thus, the way the cells interact with their environment. Often caused by chromosomal rearrangements, including gene amplifications, translocations or deletions, the altered levels of gene expression may provide a tumor-specific signature that can be exploited for diagnostic or therapeutic purposes. We investigated the utility of multiplexed fluorescence in situ hybridization (FISH) using non-isotopically labeled cDNA probes detected by Spectral Imaging as a sensitive and rapid procedure to measure tumor-specific gene expression signatures. We used a commercially available system to acquire and analyze multicolor FISH images. Initial investigations used panels of fluorescent calibration standards to evaluate the system. These experiments were followed by hybridization of five-to-six differently labeled cDNA probes, which target the transcripts of tyrosine kinase genes known to be differently expressed in normal cells and tumors of the breast or thyroid gland. The relatively simple, yet efficient, molecular cytogenetic method presented here may find many applications in characterization of solid tumors or disseminated tumor cells. Addressing tumor heterogeneity by means of multi-parameter single cell analyses is expected to enable a wide range of investigations in the areas of tumor stem cells, tumor clonality and disease progression. Full article

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Open AccessArticle

Soybean Hydrophobic Protein Response to External Electric Field: A Molecular Modeling Approach

by Ashutosh Singh, Valérie Orsat and Vijaya Raghavan

Biomolecules 2013, 3(1), 168-179; https://doi.org/10.3390/biom3010168 - 11 Feb 2013

Cited by 85 | Viewed by 9039

Abstract

The molecular dynamic (MD) modeling approach was applied to evaluate the effect of an external electric field on soybean hydrophobic protein and surface properties. Nominal electric field strengths of 0.002 V/nm and 0.004 V/nm had no major effect on the structure and surface [...] Read more.

The molecular dynamic (MD) modeling approach was applied to evaluate the effect of an external electric field on soybean hydrophobic protein and surface properties. Nominal electric field strengths of 0.002 V/nm and 0.004 V/nm had no major effect on the structure and surface properties of the protein isolate but the higher electric field strength of 3 V/nm significantly affected the protein conformation and solvent accessible surface area. The response of protein isolate to various external field stresses demonstrated that it is necessary to gain insight into protein dynamics under electromagnetic fields in order to be able to develop the techniques utilizing them for food processing and other biological applications. Full article

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Open AccessReview

MicroRNA Expression in Cystic Fibrosis Airway Epithelium

by Catherine M. Greene

Biomolecules 2013, 3(1), 157-167; https://doi.org/10.3390/biom3010157 - 11 Feb 2013

Cited by 5 | Viewed by 5576

Abstract

MicroRNAs (miRs) have emerged as major regulators of the protein content of a cell. In the most part, miRs negatively regulate target mRNA expression, with sets of miRs predicted to regulate certain signaling pathways. The miR expression profile of endobronchial brushings is altered [...] Read more.

MicroRNAs (miRs) have emerged as major regulators of the protein content of a cell. In the most part, miRs negatively regulate target mRNA expression, with sets of miRs predicted to regulate certain signaling pathways. The miR expression profile of endobronchial brushings is altered in people with cystic fibrosis (CF) compared to those without CF. How this impacts on CF has important implications for our growing understanding of the pathophysiology of CF lung disease and the development of new therapeutics to treat its pulmonary manifestations. Herein we discuss the potential consequences of altered miR expression in CF airway epithelium particularly with respect to cystic fibrosis transmembrane conductance regulator (CFTR) expression, innate immunity and toll-like receptor signalling and explore how best to exploit these changes for therapeutic benefit. Full article

(This article belongs to the Special Issue Non-coding RNA)

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Open AccessReview

Why YRNAs? About Versatile RNAs and Their Functions

by Marcel Köhn, Nikolaos Pazaitis and Stefan Hüttelmaier

Biomolecules 2013, 3(1), 143-156; https://doi.org/10.3390/biom3010143 - 8 Feb 2013

Cited by 39 | Viewed by 10139

Abstract

Y RNAs constitute a family of highly conserved small noncoding RNAs (in humans: 83-112 nt; Y1, Y3, Y4 and Y5). They are transcribed from individual genes by RNA-polymerase III and fold into conserved stem-loop-structures. Although discovered 30 years ago, insights into the cellular [...] Read more.

Y RNAs constitute a family of highly conserved small noncoding RNAs (in humans: 83-112 nt; Y1, Y3, Y4 and Y5). They are transcribed from individual genes by RNA-polymerase III and fold into conserved stem-loop-structures. Although discovered 30 years ago, insights into the cellular and physiological role of Y RNAs remains incomplete. In this review, we will discuss knowledge on the structural properties, associated proteins and discuss proposed functions of Y RNAs. We suggest Y RNAs to be an integral part of ribonucleoprotein networks within cells and could therefore have substantial influence on many different cellular processes. Putative functions of Y RNAs include small RNA quality control, DNA replication, regulation of the cellular stress response and proliferation. This suggests Y RNAs as essential regulators of cell fate and indicates future avenues of research, which will provide novel insights into the role of small noncoding RNAs in gene expression. Full article

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509 KiB

Open AccessReview

Regulation of Mammalian Gene Dosage by Long Noncoding RNAs

by Ko-Hsuan Hung, Yang Wang and Jing Crystal Zhao

Biomolecules 2013, 3(1), 124-142; https://doi.org/10.3390/biom3010124 - 4 Feb 2013

Cited by 3 | Viewed by 9676

Abstract

Recent transcriptome studies suggest that long noncoding RNAs (lncRNAs) are key components of the mammalian genome, and their study has become a new frontier in biomedical research. In fact, lncRNAs in the mammalian genome were identified and studied at particular epigenetic loci, including [...] Read more.

Recent transcriptome studies suggest that long noncoding RNAs (lncRNAs) are key components of the mammalian genome, and their study has become a new frontier in biomedical research. In fact, lncRNAs in the mammalian genome were identified and studied at particular epigenetic loci, including imprinted loci and X-chromosome inactivation center, at least two decades ago—long before development of high throughput sequencing technology. Since then, researchers have found that lncRNAs play essential roles in various biological processes, mostly during development. Since much of our understanding of lncRNAs originates from our knowledge of these well-established lncRNAs, in this review we will focus on lncRNAs from the X-chromosome inactivation center and the Dlk1-Dio3 imprinted cluster as examples of lncRNA mechanisms functioning in the epigenetic regulation of mammalian genes. Full article

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682 KiB

Open AccessArticle

Application of Metabolic ¹³C Labeling in Conjunction with High-Field Nuclear Magnetic Resonance Spectroscopy for Comparative Conformational Analysis of High Mannose-Type Oligosaccharides

by Yukiko Kamiya, Kotaro Yanagi, Toshihiko Kitajima, Takumi Yamaguchi, Yasunori Chiba and Koichi Kato

Biomolecules 2013, 3(1), 108-123; https://doi.org/10.3390/biom3010108 - 25 Jan 2013

Cited by 35 | Viewed by 8388

Abstract

High mannose-type oligosaccharides are enzymatically trimmed in the endoplasmic reticulum, resulting in various processing intermediates with exposed glycotopes that are recognized by a series of lectins involved in glycoprotein fate determination in cells. Although recent crystallographic data have provided the structural basis for [...] Read more.

High mannose-type oligosaccharides are enzymatically trimmed in the endoplasmic reticulum, resulting in various processing intermediates with exposed glycotopes that are recognized by a series of lectins involved in glycoprotein fate determination in cells. Although recent crystallographic data have provided the structural basis for the carbohydrate recognition of intracellular lectins, atomic information of dynamic oligosaccharide conformations is essential for a quantitative understanding of the energetics of carbohydrate–lectin interactions. Carbohydrate NMR spectroscopy is useful for characterizing such conformational dynamics, but often hampered by poor spectral resolution and lack of recombinant techniques required to produce homogeneous glycoforms. To overcome these difficulties, we have recently developed a methodology for the preparation of a homogeneous high mannose-type oligosaccharide with ¹³C labeling using a genetically engineered yeast strain. We herein successfully extended this method to result in the overexpression of ¹³C-labeled Man₉GlcNAc₂ (M9) with a newly engineered yeast strain with the deletion of four genes involved in N-glycan processing. This enabled high-field NMR analyses of ¹³C-labeled M9 in comparison with its processing product lacking the terminal mannose residue ManD2. Long-range NOE data indicated that the outer branches interact with the core in both glycoforms, and such foldback conformations are enhanced upon the removal of ManD2. The observed conformational variabilities might be significantly associated with lectins and glycan-trimming enzymes. Full article

(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)

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984 KiB

Open AccessArticle

Binding of Sperm to the Zona Pellucida Mediated by Sperm Carbohydrate-Binding Proteins is not Species-Specific in Vitro between Pigs and Cattle

by Kazuya Takahashi, Kazuhiro Kikuchi, Yasuomi Uchida, Saeko Kanai-Kitayama, Reiichiro Suzuki, Reiko Sato, Kazunori Toma, Masaya Geshi, Satoshi Akagi, Minoru Nakano and Naoto Yonezawa

Biomolecules 2013, 3(1), 85-107; https://doi.org/10.3390/biom3010085 - 25 Jan 2013

Cited by 18 | Viewed by 9224

Abstract

Carbohydrates are candidates for the basis of species-selective interaction of gametes during mammalian fertilization. In this study, we sought to clarify the roles of sugar residues in the species-selective, sperm–oocyte interaction in pigs and cattle. Acrosome-intact porcine and bovine sperm exhibited their strongest [...] Read more.

Carbohydrates are candidates for the basis of species-selective interaction of gametes during mammalian fertilization. In this study, we sought to clarify the roles of sugar residues in the species-selective, sperm–oocyte interaction in pigs and cattle. Acrosome-intact porcine and bovine sperm exhibited their strongest binding affinities for β-Gal and α-Man residues, respectively. Porcine-sperm specificity changed from β-Gal to α-Man after the acrosome reaction, while bovine-sperm specificity did not. Binding of acrosome-intact and acrosome-reacted sperm decreased after trypsinization, indicating that the carbohydrate-binding components are proteins. While immature oocytes bound homologous sperm preferentially to heterologous sperm, oocytes matured in vitro bound similar numbers of homologous and heterologous sperm. Lectin staining revealed the aggregation of α-Man residues on the outer surface of the porcine zona during maturation. In both species, zona-free, mature oocytes bound homologous sperm preferentially to heterologous sperm. The lectin-staining patterns of the zona pellucida and zona-free oocytes coincided with the carbohydrate-binding specificities of acrosome-intact and acrosome-reacted sperm, respectively, supporting the involvement of carbohydrates in gamete recognition in pigs and cattle. These results also indicate that sperm-zona pellucida and sperm–oolemma bindings are not strictly species-specific in pigs and cattle, and further suggest that sperm penetration into the zona and/or fusion with oolemma may be species-specific between pigs and cattle. Full article

(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)

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397 KiB

Open AccessReview

Role of the Checkpoint Clamp in DNA Damage Response

by Mihoko Kai

Biomolecules 2013, 3(1), 75-84; https://doi.org/10.3390/biom3010075 - 16 Jan 2013

Cited by 8 | Viewed by 7733

Abstract

DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. [...] Read more.

DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen)-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR). Full article

(This article belongs to the Special Issue DNA Damage Response)

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330 KiB

Open AccessCorrection

Correction: Kousholt, A.N. et al. Pathways for Genome Integrity in G2 Phase of the Cell Cycle. Biomolecules 2012, 2, 579-607

by Arne Nedergaard Kousholt, Tobias Menzel and Claus Storgaard Sørensen

Biomolecules 2013, 3(1), 72-74; https://doi.org/10.3390/biom3010072 - 15 Jan 2013

Cited by 1 | Viewed by 4978

Abstract

We have discovered an error in our paper published in Biomolecules [1], in Figure 1 on page 589. The protein names ATR and ATRIP have been swapped. A corrected version of the Figure 1 is provided below. [...] Full article

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Open AccessReview

Homologous Recombination as a Replication Fork Escort: Fork-Protection and Recovery

by Audrey Costes and Sarah A. E. Lambert

Biomolecules 2013, 3(1), 39-71; https://doi.org/10.3390/biom3010039 - 27 Dec 2012

Cited by 56 | Viewed by 15401

Abstract

Homologous recombination is a universal mechanism that allows DNA repair and ensures the efficiency of DNA replication. The substrate initiating the process of homologous recombination is a single-stranded DNA that promotes a strand exchange reaction resulting in a genetic exchange that promotes genetic [...] Read more.

Homologous recombination is a universal mechanism that allows DNA repair and ensures the efficiency of DNA replication. The substrate initiating the process of homologous recombination is a single-stranded DNA that promotes a strand exchange reaction resulting in a genetic exchange that promotes genetic diversity and DNA repair. The molecular mechanisms by which homologous recombination repairs a double-strand break have been extensively studied and are now well characterized. However, the mechanisms by which homologous recombination contribute to DNA replication in eukaryotes remains poorly understood. Studies in bacteria have identified multiple roles for the machinery of homologous recombination at replication forks. Here, we review our understanding of the molecular pathways involving the homologous recombination machinery to support the robustness of DNA replication. In addition to its role in fork-recovery and in rebuilding a functional replication fork apparatus, homologous recombination may also act as a fork-protection mechanism. We discuss that some of the fork-escort functions of homologous recombination might be achieved by loading of the recombination machinery at inactivated forks without a need for a strand exchange step; as well as the consequence of such a model for the stability of eukaryotic genomes. Full article

(This article belongs to the Special Issue DNA Damage Response)

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Open AccessArticle

Comparative Ultrastructure and Carbohydrate Composition of Gastroliths from Astacidae, Cambaridae and Parastacidae Freshwater Crayfish (Crustacea, Decapoda)

by Gilles Luquet, María S. Fernández, Aïcha Badou, Nathalie Guichard, Nathalie Le Roy, Marion Corneillat, Gérard Alcaraz and José L. Arias

Biomolecules 2013, 3(1), 18-38; https://doi.org/10.3390/biom3010018 - 21 Dec 2012

Cited by 15 | Viewed by 10539

Abstract

Crustaceans have to cyclically replace their rigid exoskeleton in order to grow. Most of them harden this skeleton by a calcification process. Some decapods (land crabs, lobsters and crayfish) elaborate calcium storage structures as a reservoir of calcium ions in their stomach wall, [...] Read more.

Crustaceans have to cyclically replace their rigid exoskeleton in order to grow. Most of them harden this skeleton by a calcification process. Some decapods (land crabs, lobsters and crayfish) elaborate calcium storage structures as a reservoir of calcium ions in their stomach wall, as so-called gastroliths. For a better understanding of the cyclic elaboration of these calcium deposits, we studied the ultrastructure of gastroliths from freshwater crayfish by using a combination of microscopic and physical techniques. Because sugars are also molecules putatively involved in the elaboration process of these biomineralizations, we also determined their carbohydrate composition. This study was performed in a comparative perspective on crayfish species belonging to the infra-order Astacidea (Decapoda, Malacostraca): three species from the Astacoidea superfamily and one species from the Parastacoidea superfamily. We observed that all the gastroliths exhibit a similar dense network of protein-chitin fibers, from macro- to nanoscale, within which calcium is precipitated as amorphous calcium carbonate. Nevertheless, they are not very similar at the molecular level, notably as regards their carbohydrate composition. Besides glucosamine, the basic carbohydrate component of chitin, we evidenced the presence of other sugars, some of which are species-specific like rhamnose and galacturonic acid whereas xylose and mannose could be linked to proteoglycan components. Full article

(This article belongs to the Special Issue Challenges in Glycan, Glycoprotein and Proteoglycan Research)

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414 KiB

Open AccessReview

Molecular Insights into Poly(ADP-ribose) Recognition and Processing

by Roko Žaja, Andreja Mikoč, Eva Barkauskaite and Ivan Ahel

Biomolecules 2013, 3(1), 1-17; https://doi.org/10.3390/biom3010001 - 21 Dec 2012

Cited by 39 | Viewed by 10766

Abstract

Poly(ADP-ribosyl)ation is a post-translational protein modification involved in the regulation of important cellular functions including DNA repair, transcription, mitosis and apoptosis. The amount of poly(ADP-ribosyl)ation (PAR) in cells reflects the balance of synthesis, mediated by the PARP protein family, and degradation, which is [...] Read more.

Poly(ADP-ribosyl)ation is a post-translational protein modification involved in the regulation of important cellular functions including DNA repair, transcription, mitosis and apoptosis. The amount of poly(ADP-ribosyl)ation (PAR) in cells reflects the balance of synthesis, mediated by the PARP protein family, and degradation, which is catalyzed by a glycohydrolase, PARG. Many of the proteins mediating PAR metabolism possess specialised high affinity PAR-binding modules that allow the efficient sensing or processing of the PAR signal. The identification of four such PAR-binding modules and the characterization of a number of proteins utilising these elements during the last decade has provided important insights into how PAR regulates different cellular activities. The macrodomain represents a unique PAR-binding module which is, in some instances, known to possess enzymatic activity on ADP-ribose derivatives (in addition to PAR-binding). The most recently discovered example for this is the PARG protein, and several available PARG structures have provided an understanding into how the PARG macrodomain evolved into a major enzyme that maintains PAR homeostasis in living cells. Full article

(This article belongs to the Special Issue DNA Damage Response)

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Biomolecules, Volume 3, Issue 1 (March 2013) – 15 articles , Pages 1-269

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