The Many Functions Of Atpdependent Chromatin Remodelling Factors

Given that around 80 of nuclear DNA is packaged by nucleosomes, it is not surprising that ATP-dependent chromatin remodelling factors function in all processes involving DNA such as transcription, replication, recombination and repair (reviewed in Corona and Tamkun, 2004). They affect transcription by changing the accessibility of transcription factors to genes leading either to activation or repression. A compelling link with transcriptional repression has emerged with the discovery of the...

Epigenetic Basis Of Disease

The previous section lists and enumerates the importance of the different groups of proteins that serve to establish the epigenetic code of gene transcription. As discussed before, the cross talk between the different epigenetic marks forms the basis for a tight regulation of gene expression and thereby sets a stage for the controlled maintenance of cellular functions. Thus the integrity and stability of epigenetic gene regulation is necessary for cellular homeostasis. Perturbations to this...

Hmt

Mutations of the CBP locus were reported to be the genetic basis for Rubinstein-Taybi syndrome, a developmental haploinsufficiency disorder (Petrij et al., 1995). Patients with this syndrome exhibit an increased risk of developing malignant tumors at an early age with symptoms of wide thumbs, broad toes, craniofacial defects, and mental retardation (Murata etal., 2001 Gibbons, 2005). Mutations of the p300 locus have also been detected in primary solid tumors and tumor cell lines of epithelial...

Marbps And Disease Manifestation

Diet Cure Lipomas

Since most cases of malignant transformations occur by means of deregulation of genes or viral integrations, the role of MARs and MARBPs become crucial. The composition of nuclear matrix has been reported to be altered during the course of transformation and the MARBPs that associate with transcriptional units might be involved in the progression cessation of disease. The uncontrolled cell proliferation and invasion of the cancer cells would naturally require an altered organization of the...

The Histone H3 Variant Nucleosomes

The two major histone variants of H3, CENP-A (centromeric protein A) and H3.3, are the object of several studies. CENP-A is present in all eukaryotes and it has different names (Kamakaka and Biggins, 2005), but here for simplicity we will use the name CenH3 (centromeric H3) for this protein. CenH3 is specifically localized to the centromeres and it replaces the canonical H3 in the centromeric chromatin (Palmer et al, 1989, 1990). The CenH3 gene is essential and its disruption resulted in very...

Variants Of The Histone H2a

Histone H2a Structure

Variants of histone H2A are most common in higher eukaryotes. Thus far, five H2A-type histones have been described, of which two are found in all eukaryotes from yeast to mammals Table 1 . These are the histones H2A.X, and H2A.Z Thatcher and Gorovsky 1994 . While all other eukaryotes possess a canonical H2A, S. cerevisiae utilizes H2A.X as general, replication-dependent H2A form. Vertebrates possess an additional H2A variant named macroH2A, while the fifth known H2A variant H2ABBd Barr...

Association Of Anticancer Drugs With Dna At The Chromatin Level

Dna Intercalation Bisanthracyclin

There have been two basic approaches. First one involves isolation of the chromatin and nucleosome from the healthy and diseased cell line. The second approach is the reconstitution of the model target such as nucleosome followed by the association with the drug s . The second approach has been extensively employed to identify the binding site in the protein-nucleic acid complex. A pre-knowledge about the components and their arrangements in the reconstituted system sometime makes it the...

Tip60

The Tat-interacting protein of 60 kDa Tip60 was originally identified through a yeast two-hybrid screen as a binding partner of the HIV1 Tat protein Kamine et al., 1996 . It is the catalytic subunit of the evolutionarily conserved NuA4 Nucleosome Acetyltransferase of histone H4 complex Fig. 1b , which in humans also notably contains the p400 ATP-dependent chromatin remodeler and the catalyt-ically inactive TRRAP PI3-kinase-like kinase Doyon and Cote, 2004 Doyon et al., 2006 . The NuA4 complex...

Chromatin Structures And Dynamics

Hp1 Nuclear Membrane Pombe

Nucleosome - The Most Fundamental Structural Unit of Chromatin The most fundamental and well-characterized structural unit of the chromosome is the nucleosome Kornberg, 1974 McGhee and Felsenfeld, 1980 . The nucle-osome chromatin structures play critical roles in the regulation of various genomic events the nucleosome restricts the access of regulatory proteins and prevents the progress of enzymatic reactions along the DNA Felts et al., 1990 O'Neill et al., 1992 . Not only the nucleosome...

References

Allain FH, Bouvet P, Dieckmann T, Feigon J 2000a Molecular basis of sequence-specific recognition of pre-ribosomal RNA by nucleolin. Embo J 19 6870-6881 Allain FH, Gilbert DE, Bouvet P, Feigon J 2000b Solution structure of the two N-terminal RNA-binding domains of nucleolin and NMR study of the interaction with its RNA target In Process Citation . J Mol Biol 303 227-241 Alvarez M, Quezada C, Navarro C, Molina A, Bouvet P, Krauskopf M, Vera MI 2003 An increased expression of nucleolin is...

Neurodegenerative Diseases And Apoptosis

Neuronal apoptosis is a process that naturally occurs during development of the brain, as more neurons than needed are originally produced and those which are not correctly connected will die in order to set the proper number of neurons to form a functional network. Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Neurological symptoms will depend of which neuronal...

Role Of Non Histone Proteins Acetylation On Cellular Function

Histone Proteins Function

Reversible acetylation of histone and nonhistone proteins play key role in maintaining cellular homeostasis. In this following section we shall discuss about the physiological significances of acetylation and deacetylation of different classes of nonhistone proteins. 2.1. Chromatin Dynamics and Transcription Nonhistone chromatin proteins are integral structural components of the chromatin. The dynamicity of the chromatin is maintained by chromatin compaction leading to higher order structure...

P713t

Moz Cbp Fusion

Cell line Primary Primary Cell line Cell line Cell line Gayther et al., 2000 Gayther et al., 2000 Koshiishi et al., 2004 Bryan et al., 2002 Bryan et al., 2002 Gayther et al., 2000 Gayther et al., 2000 Bryan et al., 2002 Bryan et al., 2002 Shigeno et al., 2004 Ohshima etal, 2001 Ozdag et al., 2002 Ozdag et al., 2002 a Shown are nonsense, missense, deletion insertion and splice site mutations. b The amino acid changes are predictions in many cases. c X denotes a stop codon. d Originally annotated...

Nucleolin As A Protooncogene That Stimulates Cell Proliferation

It has been shown that in cancer cell lines characterized by different proliferation rates, the transcriptional activity of RNA polymerase I and the expression of the major nucleolar proteins involved in the control of rRNA transcription and processing are directly related to nucleolar size and to the rapidity of cell proliferation Derenzini et al., 1998 . Several observations suggest that nucleolin is a major actor in promoting cell proliferation. First of all, its amount is correlated with...

Non Histone Protein Acetylation Link To Diseases

Pathways Thyroid Hormone Receptors

Aberrant acetylation levels of non histone proteins not only lead to the dysfunction of these proteins but also cause disturbances in cellular processes thereby leading to several diseases Fig. 3 . There are several reports of aberrant acetylation in diseases like cancer, diabetes, cardiac hypertrophy and viral diseases. Diabetes is hypothesized to cause cardiac protein acetylation and the acety-lation alters the protein function Fig. 3b . Hypoxia-inducible factor-1 HIF1 is a transcription...

Molecular And Structural Basis Of Dnabinding Anticancer Drug Action

Anticancer drugs targeted to DNA bind to the same by either non-covalent forces or covalent interactions. The primary and most important step in the functioning of a DNA targeting drug is the base-specific recognition of DNA by the drug. This initial process of recognition is driven by size and shape complementarities between the drug and its DNA - binding site. Non-covalent forces such as the coulombic force, van der Waals interactions, hydrogen bonding and stacking interaction stabilize the...

Parp1 As A Therapeutic Target In Disease

Role of PARP-1 in Physiological and Pathophysiological Processes Genome Maintenance, Cell Death, and Inflammation PARP-1 has been implicated in a variety of physiological and pathophysiological processes, including genome maintenance, carcinogenesis, aging, immunity, inflammation, and neurological function Kim et al., 2005 Table 2 . PARP-1's roles in DNA repair, cell death pathways, and pro-inflammatory gene expression underlie many of the contributions PARP-1 makes to the aforementioned...