DNA
Chapters
« previous | page 2 of 3 pages | next »NAD-metabolism and Regulatory Functions
Mathias Ziegler
Poly-ADP-ribosylation has turned out to be a major NAD-consuming process in most eukaryotic cells. Although PARP1 exhibits by far the highest capacity to synthesise poly-ADP-ribose, it is active only in situations that are accompanied by DNA damage. It would appear therefore that, under normal ph...
Non-Long Terminal Repeat Retrotransposons Colonizing Schistosome Genomes
Thewarach Laha, Claudia S. Copeland and Paul J. Brindley
It has become apparent that the schistosome genome is replete with numerous copies of diverse repetitive sequences. Mobile genetic elements constitute much of this repetitive component of the schistosome genome. Of these mobile elements, an expanding number of discrete schistosome retrotranspo...
Orchestration of Telomeres and DNA Repair Factors in Mammalian Cells Implications for Cancer and Ageing
M. Prakash Hande
Loss of telomere homeostasis via chromosome-genomic instability might effectively pro mote tumour progression. Telomere function may have contrasting roles: inducing rep licative senescence and promoting tumourigenesis and these roles may vary between cell types depending on the expression of tel...
Parp and Epigenetic Regulation
Paola Caiafa
In the post-genome era attention is being focused on those epigenetic modifications which modulate chromatin structure to guarantee that information present on DNA is read correctly and at the most appropriate time in order to meet cellular requirements. In this chapter data are reviewed which sh...
PARP and the Release of Apoptosis-Inducing Factor from Mitochondria
Suk Jin Hong, Ted M. Dawson and Valina L. Dawson
Death is the inevitable fate for all living things including individual cells. However, untimely death results in dysfunction and disease. Understanding the normal regulation of cell death and cell survival is critical for the development of successful therapies for preventing and treating diseas...
PARP Inhibitors and Cancer Therapy
Nicola J. Curtin
The compelling evidence for the role of poly(ADP-ribose) polymerase(s) (PARP) in the cellular reaction to genotoxic stress was the stimulus to develop inhibitors as therapeu tic agents to potentiate DNA-damaging anticancer therapies. The earliest inhibitors, the benzamides, developed in the 1980s...
PARP-1 and the Shape of Cell Death
Laslo Virag
The following review discusses the mechanisms through which cell death may be regu lated by poly(ADP-ribose) polymerase-1(PARP-1), a nuclear enzyme that catalyzes the synthesis of long, branching (ADP-ribose)n polymers from NAD+. Cell death may be caused by nongenotoxic or genotoxic stimuli. Wher...
PARP-1 As Novel Coactivator of NF-kB in Inflammatory Disorders
Paul O. Hassa and Michael O. Hottiger
Mammalian poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin associated protein and belongs to a large family of enzymes that can synthesize large branched polymers of ADP-ribose units by using k-nicotinamide adenine dinucleotide (NAD+) as substrate. A pathophysiological role for PARP...
PARP-2: Structure-Function Relationship
Valérie Schreiber, Michelle Ricoul, Jean-Christophe Amé, Françoise Dantzer, Véronique Meder, Catherine Spenlehauer, Patrick Stiegler, Claude Niedergang, Laure Sabatier,Vincent Favaudon, Josiane Menissier-de Murcia and Gilbert de Murcia
Poly(ADP-ribosyl)ation is an immediate DNA damage-dependent posttranslational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a large family of 18 proteins, encoded by differen...
Poly(ADP-ribose) Polymerase (PARP) and Excitotoxicity
Domenico E. Pellegrini-Giampietro, Alberto Chiarugi and Flavio Moroni
Neuronal injury resulting from glutamate receptor-mediated excitotoxicity has been implicated in a wide spectrum of neurological disorders. Following dramatic results in the preclinical setting, anti-excitotoxic neuroprotective agents have been used in clinical trials for stroke and head injury, ...
Poly(ADP-ribose) Polymerase and Ischemia-Reperfusion Injury
Prabal K. Chatterjee and Christoph Thiemermann
Poly (adenosine 5'-diphosphate ribose) polymerase-1 (PARP-1) is an abundant chromatin-bound enzyme which is present in the nuclei of most cells. The physiological role of PARP-1 involves its activation by single strand breaks in DNA after which it transfers ADP-ribose moieties from nicotinamide a...
Poly(ADP-Ribosyl)ation and Aging
Sascha Beneke and Alexander Bürkle
In this Chapter, we review the evidence suggesting that the family of poly(ADP-ribose) polymerases (PARPs) is involved in regulation of the aging process. First, as genotoxic stress, mainly produced by reactive oxygen species, is believed to be the major driving force of cellular aging, the impor...
Preclinical and Clinical Studies on 5-Aza-2'-Deoxycytidine, a Potent Inhibitor of DNA Methylation, in Cancer Therapy
Richard L. Momparler
The preclinical and clinical investigations by the author on the antineoplastic activity of 5-Aza-2'-deoxycytidine (5AZA), a potent inhibitor of DNA methylation are reviewed. These include studies on the molecular, cellular and animal pharmacology of 5AZA. These preclinical studies indicated that...
Purine Analogues and Their Role in Methylation and Cancer Chemotherapy
Katherine L. Seley and Sylvester L. Mosley
Despite promising leads in the search for new chemotherapeutic agents, there remains an urgent need to develop more effective and less toxic drugs. Nucleosides and their corresponding nucleobases are the fundamental building blocks of many biological systems1-3 and as a result, have been extensiv...
Radiosensitivity of Cells Derived From Down Syndrome Patients: Is Defective DNA Repair Involved?
Adayapalam T. Natarajan
Down’s syndrome (DS) is an autosomal recessive human disorder caused by an extra copy of chromosome 21. DS patients are characterized by dwarfism and mental re tardation accompanied by an increased incidence of cancer development in various tissues and organs. DS patients also show signs of pre...
Radiosensitivity of Cells Derived From Down Syndrome Patients: Is Defective DNA Repair Involved?
Adayapalam T. Natarajan
Down’s syndrome (DS) is an autosomal recessive human disorder caused by an extra copy of chromosome 21. DS patients are characterized by dwarfism and mental re tardation accompanied by an increased incidence of cancer development in various tissues and organs. DS patients also show signs of pre...
Regulation of DNA Methyltransferases in Cancer
Nancy Detich and Moshe Szyf
The DNA methyltransferases (DNMTs) are critical proteins involved in establishing proper control of epigenetic information. They are responsible for maintaining the cell’s methylation pattern, as well for transcriptional repression through both methylation dependent and independent mechanisms. ...
Retrotransposons in the Genomes of the Digenean Parasitic Trematodes, Clonorchis sinensis and Paragonimus westermani
Young-An Bae and Yoon Kong
Considerable fractions of almost all eukaryotic genomes are composed of a variety of transposable elements (TEs). Members of the phylum Platyhelminthes are also thought to contain diverse TEs which comprise up to 40% of their genomes. A total of 29 retrotransposons, positioning into one non-long-...
Role of Poly (ADP-ribose) Polymerase Activation in the Pathogenesis of Inflammation and Circulatory Shock Poly (ADP-ribose) Polymerase and Shock and Inflammation
Csaba Szabo
Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Activation of PARP may dra matically lower the intracellular concentration of its substrate, nicotinamide adenine dinucleotide, thus slowing the rate of glyco...
Role of Poly-ADP-Ribosylation in Cancer Development
Mitsuko Masutani, Akemi Gunji, Masahiro Tsutsumi, Kumiko Ogawa, Nobuo Kamada, Tomoyuki Shirai, Kou-ichi Jishage, Hitoshi Nakagama and Takashi Sugimura
Elucidation of the relationship between poly-ADP-ribosylation and carcinogenesis has markedly progressed by the recent development of knockout or transgenic mice models of poly(ADP-ribose) polymerase (Parp)-1, Parp-2, and poly(ADP-ribose) glycohydrolase (Parg). Parp-1 is involved in base excision...
Roles of Poly(ADP-Ribose) Metabolism in the Regulation of Centrosome Duplication and in the Maintenance of Neuronal Integrity
Masanao Miwa, Masayuki Kanai, Masahiro Uchida, Kazuhiko Uchida and Shuji Hanai
The chemical structure of poly(ADP-ribose) suggests not only that its modification of acceptor proteins should modify the structure and function of the acceptor proteins, but also that the poly(ADP-ribose) molecule itself should possess an intrinsic structural information that can alter cellular ...
Roles of the BRCA1 and BRCA2 Breast Cancer Susceptibility Proteins in DNA Repair
Katrin Gudmundsdottir, Emily Witt and Alan Ashworth
Since the cloning of the BRCA1 and BRCA2 genes less than 10 years ago, a great deal of effort has been expended in attempting to uncover the functions of the encoded proteins. BRCA1 and BRCA2 have now been linked to a wide variety of cellular functions through binding or colocalization with other...
Schistosome DNA Transposons
Ricardo DeMarco and Sergio Verjovski-Almeida
Schistosomes are digenetic blood flukes and the causative agents of schistosomiasis in humans. Large transcriptome and genome sequence databases have recently become publicly available for Schistosoma mansoni and S. japonicum and have provided a comprehensive repository for the discovery of ...
Schistosome Long Terminal Repeat Retrotransposons
Claudia S. Copeland, Thewarach Laha and Paul J. Brindley*
The human schistosomes, blood flukes of the Genus Schistosoma, have a large genome estimated to be at least 270 megabase pairs (haploid) in size, arrayed on eight pairs (2n = 16) of chromosomes including the Z (male) and W (female) sex chromosomes. The genome appears to include about 14,000 prote...
Schistosome Long Terminal Repeat Retrotransposons
Claudia S. Copeland, Thewarach Laha and Paul J. Brindley
The human schistosomes, blood flukes of the Genus Schistosoma, have a large genome estimated to be at least 270 megabase pairs (haploid) in size, arrayed on eight pairs (2n = 16) of chromosomes including the Z (male) and W (female) sex chromosomes. The genome appears to include about 14,000 prote...
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