Begell House Inc.
Critical Reviews™ in Eukaryotic Gene Expression
CRE
1045-4403
15
4
2005
Linkage of Lamins to Fidelity of Gene Transcription
277-294
10.1615/CritRevEukarGeneExpr.v15.i4.10
Nadir M.
Maraldi
ITOI-CNR, Unit of Bologna, c /o IOR, Via di Barbiano 1/10; Laboratory of Biologia Cellulare e Microscopia Elettronica, IOR; and Department of Scienze Anatomiche Umane e Fisiopatologia Apparato Locomotore, University of Bologna, Italy
Giovanna
Lattanzi
ITOI-CNR, Unit of Bologna, c /o IOR, Via di Barbiano 1/10, Bologna, Italy
Two major events are emerging as being involved in the fine regulatory mechanisms that control gene expression through the nuclear envelope/lamina. The first is the linkage of envelope proteins to transcription factors, most of which function as transcriptional repressors. The second is the interplay between nuclear lamina/nuclear envelope proteins and chromatin, through more or less direct interactions with DNA-binding proteins. The first mechanism appears to play a major role in tissue-specific functions, whereas the latter mechanism likely modifies higher-order chromatin organization, thus regulating differentiation and aging. This review highlights the importance of the study of a group of genetic diseases, collectively referred to as laminopathies, to understand the actual role played by lamins in ensuring the fidelity of gene expression and in modulating cеll differentiation.
Measuring DNA Nucleobase Adducts Using Neutral Hydrolysis and Liquid Chromatography-Mass Spectrometry
295-316
10.1615/CritRevEukarGeneExpr.v15.i4.20
Maricar
Tarun
Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060
James F.
Rusling
Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060; Department of Pharmacology, University of Connecticut Health Center, Farmington, CT 06032
The detection and identification of DNA adducts is important for predicting human cancer risk posed by chemicals and for uncovering potential genotoxicity of new drug and agricultural chemical candidates. For compounds that react with DNA to form N7-guanine and/or N3-adenine adducts, neutral thermal hydrolysis provides a simple procedure for sample preparation. The N7-guanine and N3-adenine adducts are selectively ejected from the DNA chain, resulting in a clean sample matrix enriched in nucleobase adducts. Coupling neutral thermal hydrolysis with liquid chromatography-mass spectrometry (LC-MS) provides sensitive methods to detect and quantitate DNA adducts, and structural information is provided by MS. Combining these technologies with capillary liquid chromatography sample preconcentration systems can provide exquisitely sensitive detection. In this review, we first summarize the chemistry of nucleobase adduct formation, briefly summarize modern methods to detect DNA adducts, and then describe neutral thermal hydrolysis coupled to LC-MS/MS and some of its applications to DNA damage studies. Finally, we review recent applications of neutral thermal hydrolysis and LC-MS to toxicity screening of chemicals.
Polymeric Gene Carriers
317-342
10.1615/CritRevEukarGeneExpr.v15.i4.30
Han Chang
Kang
Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, USA
Minhyung
Lee
Department of Bioengineering, College of Engineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Korea
You Han
Bae
Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, USA
Polymeric gene carriers are a potential alternative to using viral vectors. Polymeric carriers have relatively low immunogenicity and cytotoxicity. In addition, polymeric carriers can accommodate large-size DNA, be conjugated with appropriate functionalities, and be administered repeatedly. In spite of these advantages, polymeric gene carriers have some limitations, such as low gene transfection efficiencies and relatively short duration of gene expression. Therefore, extensive research has been conducted toward the development of efficient polymeric carriers. In this review, we discuss current problems associated with polymeric gene carriers and various strategies against transfection barriers—in particular, gene stabilization and protection, cellular targeting, endosomal escaping, nuclear targeting, unpackaging, and biocompatibility. Finally, requirements for future polymeric gene carriers are considered. With all these ongoing efforts, polymeric carriers have become one of the promising gene delivery methods for human gene therapy.
Age-Dependent Biomechanical Modifications in Bone
343-358
10.1615/CritRevEukarGeneExpr.v15.i4.40
Deepak
Vashishth
Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute
Age-related nontraumatic fractures are a major public health problem. Even though lower bone mass is the most commonly implicated variable for the age-related increase in fracture incidence, studies show that the resistance of bone material against fracture (toughness) diminishes with age. The mechanisms for the age-related loss of toughness are, however, unknown and may involve alterations in the quality of the bone material. The review of literature presented here identifies changes in the quality of bone material at ultrastructural, lamellar, osteonal, and tissue levels as plausible contributors to the biomechanical changes in aging human bone. The changes in bone quality at these multiple levels of organization result in a systematic breakdown of the mechanical and biological mechanisms that provide bone with its resistance against fracture. Animal studies conducted to date suggest that, similar to bone mass, bone quality may be partially regulated by genetics.
Indexes
359-361
10.1615/CritRevEukarGeneExpr.v15.i4.50