DNA
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page 1 of 3 pages | next »Anticancer Gene Therapy by in Vivo DNA Electrotransfer of MBD2 Antisense
Pascal Bigey and Daniel Scherman
Harnessing the full therapeutic potential of DNA methylation machinery proteins would require efficient techniques of introducing either anti sense, iRNA or expression vectors into tumors in vivo. Efficient techniques for introducing DNA in vivo are also required for target validation. This chapt...
CpG Island Hypermethylation of Tumor Suppressor Genes in Human Cancer: Concepts, Methodologies and Uses
Michel Herranz and Manel Esteller
Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of human cancer. One of the most characteristic changes is the hypermethylation of CpG islands of tumor suppressor genes associated with their transcriptional silencing. The target genes are distributed in all cellu...
Defective Solar Protection in Xeroderma Pigmentosum and Cockayne Syndrome Patients
Colette apRhys and Daniel Judge
Xeroderma pigmentosum (XP),1 Cockayne syndrome (CS)2,3 and xeroderma pigmentosum-Cockayne syndrome (XP-CS)4,5 are rare disorders with autosomal recessive inheritance, characterized by extreme sensitivity to sunlight. This sensitivity reflects the inadequate removal and/or repair of UV-induced les...
DNA Damage Signaling through Poly(ADP-Ribose)
Maria Malanga and Felix R. Althaus
Several lines of evidence reveal that poly(ADP-ribose)polymerase-1 (PARP-1) operates in a DNA damage signaling network. Poly(ADP-ribose) metabolism induced by DNA damage participates in DNA repair and contributes to downstream mechanisms leading to cell cycle arrest, cell survival, cell death, or...
DNA Hypo- vs. Hypermethylation in Cancer: Tumor Specificity, Tumor Progression, and Therapeutic Implications
Melanie Ehrlich and Guanchao Jiang
DNA hypomethylation associated with cancer is probably as frequent as cancer-linked DNA hypermethylation. The hypomethylation of genomic sequences often exceeds hypermethylation so that cancers frequently display lower levels of genomic 5-methylcytosine than do a variety of normal postnatal tissu...
DNA Methylation in Colorectal Cancer
Jeremy R. Jass, Vicki L.J. Whitehall, Joanne Young and Barbara A. Leggett
In this chapter, it is pointed out that colorectal cancer is a heterogeneous disease. The case is made for a ‘serrated pathway’ of neoplasia that would evolve relatively rapidly through the early acquisition of DNA instability. DNA hypermethylation is likely to be of critical importance in drivin...
DNA Methylation in Urological Cancers
Wolfgang A. Schulz and Hans-Helge Seifert
Urological cancers are a diverse group with different alterations of DNA methylation. In all urological cancers, DNA hypermethylation of specific genes has been described. In contrast, methylation of repetitive sequences is often diminished, resulting in decreased overall methylation levels (“glo...
DNA Methylation: Three Decades in Search of Function
Aharon Razin
DNA methylation is an epigenetic mark that is involved in control mechanisms of a variety of biological processes. Being symmetrically positioned on the two complementary DNA strands the methyl groups represent a clonally inheritable feature of the DNA. Once established during embryogenesis, meth...
DNA Methyltransferase Inhibitors: Paving the Way for Epigenetic Cancer Therapeutics
Gregory K. Reid and A. Robert MacLeod
Our increased understanding of the molecular pathophysiology of cancer is beginning to impact our ability to effectively treat this disease. The recent success of the tyrosine kinase inhibitor Gleevec™ is a prime example of this. In this case, the molecular etiology of the disease (chronic myelog...
DNA Repair Aspects For Recq Helicase Disorders
Takehisa Matsumoto
RecQ family DNA helicases are defined by amino acid sequence similarities to Escheri chia coli RecQ which has been known to act in homologous recombination and to suppress illegitimate recombination, particularly during the repair of DNA double strand breaks. Five RecQ family genes have been iden...
Dynamic Interaction between PARP-1, PCNA and p21waf1/cip1
Ennio Prosperi and A. Ivana Scovassi
Poly(ADP-ribose) polymerase (PARP-1) plays a crucial role in DNA repair and interacts with many DNA replication/repair factors, including the Proliferating Cell Nuclear Antigen (PCNA), a protein involved in many DNA transactions. The association between these proteins in vitro results in the inhi...
Endogenous Retrotransposon Sequences of the Schistosoma mansoni Intermediate Snail Host, Biomphalaria glabrata
Matty Knight, Joanna Bridger, Wannaporn Ittiprasert, Edwin Odoemelam, Julio Masabanda, André Miller and Nithya Raghavan
Schistosomiasis remains a major public health concern in 75 countries. Disease preva- lence and transmission is intimately associated with the presence of freshwater snails that serve as intermediate hosts for the larval stage of the parasite. The discovery of retrotransposons and transposons ...
Enzymes in Poly(ADP-Ribose) Metabolism
Ralph G. Meyer , Mirella L. Meyer-Ficca, Elaine L. Jacobson and Myron K. Jacobson
Studies over many years have revealed the central importance of poly(ADP-ribose) me tabolism in the maintenance of genomic integrity. While the involvement of poly(ADP-ribose) polymerase-1 (PARP-1) in this metabolism has been long known, more recent studies have demonstrated the contribution of m...
Epigenetic Mechanisms of Gene Regulation: Relationships between DNA Methylation, Histone Modification, and Chromatin Structure
Keith D. Robertson
DNA methylation is a post-replicative, or epigenetic, modification of the genome that is critical for proper mammalian embryonic development, gene silencing, X chromosome inactivation, and imprinting. Genome-wide DNA methylation patterns are nonrandomly distributed and undergo significant remodel...
Essential Molecular Tools for Cellular Machinery Prokaryotic and Eukaryotic DNA Helicases
Narendra Tuteja and Renu Tuteja
DNA helicases are ubiquitous molecular motor proteins that harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of energetically stable duplex DNA, and thus play important roles in nearly all aspects of nucleic acid metabolism. Basically helicases break the hydrogen bonds ...
Functional Interactions of PARP-1 with p53
Rafael Alvarez-Gonzalez, Hanswalter Zentgraf, Manfred Frey and Hilda Mendoza-Alvarez
A close correlation between the frequency of specific mutations of oncogenes and/or tumor suppressor genes in mammals and cancer has been suspected for a long time. For instance, either spontaneous or forcefully inflicted mutations of a tumor suppressor gene coding for a protein known as p53 a...
Functional Interactions of PARP-1With p53 Molecular Interactions of PARP-1 With p53
Rafael Alvarez-Gonzalez, Hanswalter Zentgraf, Manfred Frey and Hilda Mendoza-Alvarez
A close correlation between the frequency of specific mutations of oncogenes and/or tumor suppressor genes in mammals and cancer has been suspected for a long time. For instance, either spontaneous or forcefully inflicted mutations of a tumor suppressor gene coding for a protein known as p53 are ...
Genome Degradation by DNAS1L3 Endonuclease: A Key PARP-1-Regulated Event in Apoptosis
A. Hamid Boulares, Alexander G. Yakovlev and Mark E. Smulson
Degradation of chromatin into internucleosomal fragments, a prevailing hallmark of apoptosis in most cells and tissues, has been tightly associated with a Ca2+ and Mg2+-dependent endonuclease activity. Several candidate enzymes have been identified as important players in this process. Several de...
Human Premature Aging Disorders and Dysfunction of DNA Repair
Byungchan Ahn and Vilhelm A. Bohr
Werner’s syndrome (WS) and Cockayne syndrome (CS) are rare human autosomal recessive disorders classified as segmental progeroid disorders. WS is marked by premature onset of age-related phenotypic changes (such as cataract and greying of hair etc) and genome instability. Cells derived from CS pa...
Identifying Clinicopathological Association of DNA Hypermethylation in Cancers Using CpG Island Microarrays
Susan H. Wei, Timothy T.-C. Yip, Chuan-Mu Chen and Tim H.-M. Huang
Hypermethylation of promoter CpG islands has been associated with gene silencing in cancer. Increasingly, these CpG islands have potential clinical utility as molecular markers for cancer diagnosis. Here we describe a microarray-based technique, called differential methylation hybridization (DMH)...
Inhibition of Poly(ADP-Ribosyl)ation Allows DNA Hypermethylation
Anna Reale, Giuseppe Zardo, Maria Malanga, Jordanka Zlatanova and Paola Caiafa
This chapter emphasizes that along the chain of events that induce DNA methylation-dependent chromatin condensation, a post-synthetic modification other than histone acetylation, poly(ADP-ribosyl)ation, participates in the establishment and maintenance of methylation-free regions of chromatin. In...
Is Ataxia Telangiectasia a Result of Impaired Coordination Between DNA Repair and Cell Cycle Checkpoint Regulators?
Adayabalam S. Balajee and Charles R. Geard
Ataxia telangiectasia (AT) is an autosomal recessive multisystem human disorder and patients are characterized by cerebellar ataxia, oculocutaneous telangiectasia, immuno deficiency, chromosomal instability and radio sensitivity with an increased predisposition to lymphoid cancer in childhood. Th...
Mechanisms of DNA Damage and Repair in Alzheimer Disease
V. Prakash Reddy, George Perry, Marcus S. Cooke, Lawrence M. Sayre and Mark A. Smith
Reactive oxygen species (ROS) are produced during the respiratory cycle in mitochon- dria,1 as well as normal cellular and xenobiotic metabolism. Exposure to various noxious insults can also lead to ROS production. In addition, ROS are also generated through metal-catalyzed reactions. A consequ...
Methylation Analysis in Cancer: (Epi)Genomic Fast Track from Discovery to Clinical Routine
Carolina Haefliger, Sabine Maier and Alexander Olek
Aberrant DNA methylation is an early and common event in human cancers. Methylation acts as an epigenetic regulator of gene expression and is involved in cancer development as well as resistance to drug treatments. Specific methylation patterns have been shown for different cancer types and there...
Mobile Genetic Elements of Malaria Vectors and Other Mosquitoes
Zhijian Tu and Song Li
Mosquitoes are important vectors of a number of disease agents including malarial and filarial parasites as well as many types of viruses. A wide spectrum of both RNA-mediated and DNA-mediated transposable elements (TEs) have been discovered in the African malaria mosquito, Anopheles gambiae, and ...
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