To pack the DNA inside the nucleus, the negatively charged DNA is wrapped around the positively charged histone protein to form a nucleosome, which is then tightly packed with other nucleosomes to form a condense chromatin (Nair and Kumar, 2012). The chromatin remodeling can change the interaction between the DNA and histones to alter the chromatin structure (Nair and Kumar, 2012). Based on how tightly the DNA is wrapped around the histone, some regions of the DNA may be either exposed or hidden, affecting the accessibility of transcriptional machinery to the regulatory sequence (Nair and Kumar, 2012). The chromatin remodeling complex uses the energy obtained from ATP to modify the chromatin structure by either moving nucleosomes along the …show more content…
BRG1/BRM-associated factor (BAF) is a human analog of SWI/SNF complex, which assists chromatin remodeling by stimulating the sliding of the nucleosome (Liu et al., 2012). BAF possesses multiple domains that are conserved in the SWI/SNF2 complex in yeast cells (Liu et al., 2012). The conservation of these complexes suggests that these two complexes are evolutionarily related in both functions and structures and that the chromatin remodeling may have played a significant role in regulating the gene expression in early eukaryotes. The common protein domains found in BAF complexes are AT-rich DNA interaction (ARID) domain, which can bind to a specific region of the DNA; bromodomain, which binds to acetylated lysines on a histone tail; and chromodomain, which binds to the methylated lysine on the histone (Nie et al., 2000; Dhalluin et al., 1999; Flanagan et al., 2005). While most BAF complexes contain major subunits, the composition of BAF complexes may vary based on their functions. For example, progenitor cells express chromatin remodeling complexes containing BAF45a subunit, but the subunit is exchanged to either BAF45b, BAF45c of BAF53b subunit for the neuronal cell proliferation and differentiation (Lessard et al., 2007). Such changes in the subunits suggest that the specificity of BAF complexes depend on its individual
Varshavsky, A.J., et al. “Compact form of SV40 Viral Minichromosome is Resistant to Nuclease: Possible Implications for Chromatin Structure.” Nucleic acids research 4 (1977): 3303-3325.
Genome: The Autobiography of A Species in 23 Chapters by Matt Ridley is an interesting book. It is written in a style that is very casual and very understandable. If someone who knew nothing about genetics or biology were to read this book, they would find it very interesting and informative. Ridley uses basic scientific terms so as not to confuse the average reader.
Histone modification may or may not be dependent on DNA methylation and is difficult to detect compared to LOH.
RNAi, DNA and chromatin modification are involved in heterochromatin formation and gene regulation and genome stability.
DNA methylation primarily occurs within sites in the DNA sequence known as CpG dinucleotides, which is a 2 base pair sequence involving a Cytosine bonded to a Guanine by a phosphodiester bond.
First, an initiator protein unwinds a short amount of the double helix. After this, the protein known as helicase, attaches to and then breaks up the hydrogen bonds between the bases of the DNA strands, therefore pulling them apart. As the helicase moves along the DNA molecule, it continues breaking the hydrogen bonds and also separating the two polynucleotide chains.
Precise chromosomal DNA replication during S phase of the cell cycle is a crucial factor in the proper maintenance of the genome from generation to generation. The current “once-per-cell-cycle” model of eukaryotic chromosome duplication describes a highly coordinated process by which temporally regulated replicon clusters are sequentially activated and subsequently united to form two semi-conserved copies of the genome. Replicon clusters, or replication domains, are comprised of individual replication units that are synchronously activated at predetermined points during S phase. Bi-directional replication within each replicon is initiated at periodic AT-rich origins along each chromosome. Origins are not characterized by any specific nucleotide sequence, but rather the spatial arrangement of origin replication complexes (ORCs). Given the duration of the S phase and replication fork rate, adjacent origins must be appropriately spaced to ensure the complete replication of each replicon. Chromatin arrangement by the nuclear matrix may be the underpinning factor responsible for ORC positioning. The six subunit ORC binds to origins of replication in an ATP-dependent manner during late telophase and early G1. In yeast, each replication domain simply contains a single ORC binding site. However, more complex origins are characterized by an initiation zone where DNA synthesis may begin at numerous locations. A single round of DNA synthesis at each activated origin is achieved by “lic...
By utilizing, and, if possible, modifying this special DNA structure, one may see a reduction of age related illness, diseases, and signs of aging. In this review of human telomeres, we will discuss the roles and functions of the telomere, its structure, and the relation of telomere length to aging and tumorigenesis. Role and Functions of The Telomeres Telomeres are special DNA structures that consist of repetitive nucleotide sequences, which serve as a “cap” to protect the ends of the chromosomes. These repetitive sequences can range from thousands of base pairs in Vertebrates to about a few hundreds of base pairs in yeast cells (Oeseburg, et al. 2009). The 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'Secondary' of the 'S Located at the ends of the chromosomes, the telomeres serve as a biological life line for cells.
“Accumulation of histone repeat transcripts in the sea urchin egg pronucleus”, Venezsky et al. Cell. 24(2):385-391.
DNA supercoiling occurs in all cells that undergo genetic processing. This event blocks replicative and transcriptional machinery from binding to the DNA helix, which proves detrimental to the cell. However, current research is beginning to show that not all affects of supercoiling produce negative results. These studies prove that different coiling patterns increase the efficiency of epigenetic processes such as methylation and acetylation. Topoisomerase, a post-transcriptional monomeric enzyme, solves the winding problem of the double helix by implementing transient cuts in the genome. As these cuts build up, the genome is essentially fragmented by the enzyme and the cell is unable to express essential genes; this genomic degradation by topoisomerase serves as a viable pathway into cancer research. This review article synthesizes the many ideas surrounding topological cellular events, and presents a new direction for research on chromatin modification in cancerous cells. However, due to the time constraints of the project, this article will not thoroughly discuss the mechanistic process of the replication pathway.
A chromosome is made up of two identical structures called chromatids. The process of nuclear division is called interphase; each DNA molecule in a nucleus makes an identical copy of itself. Each copy is contained in the chromatid and a characteristic narrow region called the centromere holds the two chromatids together. The centromere can be found anywhere along a chromosome but the position is the characteristic for a particular chromosome. Each Chromatid contains one DNA molecule. DNA is the molecule of inheritance and is made up of a series of genes. The fact that the two DNA molecules in the sister chromatids, and hence their genes, are identical is the key to precise nuclear division.
Epigenetics is the study of both heritable and non-heritable changes in gene translation, which do not stem from mutation. Epigenetic alterations to DNA may occur in several different ways; histone modification, DNA methylations, expression of microRNAs, and changes of the chromatin structure (Ntanasis-Stathopoulos et al). Depending on their presentation, they may be passed on to offspring. The exact mechanism of heritable epigenetic modification has not been discovered, but all of these alterations may have some impact on a wide range of disorders and have far reaching implications in the medical field. The study of epigenetics seeks to answer the age old question of whether nature or nurture is responsible for our phenotype, and it has arrived at the answer that in fact, both are. The discovery of epigenetic changes may lead us to cure many disorders, and even personality problems.
Citation: Philips, T. (2008) Regulation of Transcription and gene expression in Eukaryotes. Nature Education 1(1)
Thymine: Combining with Adenine this nucleobase is often replaces with uracil in RNA. It is also the common cause of mutations in DNA. When in the presence of ultraviolet light, radiation causes alterations in the DNA molecule that inhibit normal...
...ing proteins. The large protein kinase, consisting of 4128 amino acids (aa), has a molecular weight of 469 kDA (33, 85-87). DNA-PKcs associates with the Ku70/80 heterodimer and forms a catalytic active DNA-PK holoenzyme (Falck et al., 2005). The kinase activity of DNA-PKcs is activated upon interaction with a free DNA. The protein can bind to DNA fragments in absence of the Ku complex. However its kinase activity appears to be much lower (Hammarsten and Chu, 1998). DNA-PKcs mediates the synapsis and ligation of the two DNA fragments (Block et al., 2004; Kysela et al., 2005). The auto-phosphorylation of DNA-PKcs results in the remodelling of DNA-Pk (Block et al., 2004). Moreover, DNA-PK phosphorylates the histons H2AX and H1.This might indicate that DNA-PK modifies chromatin structure to facilitate the access of other DNA repair complexes to DSBs (Kysela et al., 2005