molecular biology of the cell chapter 4 summary PDF

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Chapter 4: DNA, chromosomes and genomes Molecules that carry heritable information are present in S strain cells. The hereditary information is carried in DNA. A DNA molecule consists of two complementary chains of nucleotide. bases bind together, and bases bind together. The DNA strands always bind...

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Chapter 4: DNA, chromosomes and genomes Molecules that carry heritable information are present in S strain cells. The hereditary information is carried in DNA. A DNA molecule consists of two complementary chains of nucleotide. G&C bases bind together, and A&T bases bind together. The DNA strands always bind antiparallel. The 3’ end of DNA has a hydroxyl group and the 5’ end of DNA has a phosphate group. The backbone of DNA consists of sugar and phosphate. DNA is always read from the 5’ end to the 3’ end. A DNA molecule consists of two complementary chains of nucleotides. The DNA double helix: o The bonds shown in the picture on the right are all non-covalent and weak bonds, but they are strong when there are a lot of them present. o More hydrogen bonds present means more strength. There are 3 hydrogen bonds between the G&C bases and 2 hydrogen bonds between the A&T bases. This means G&C bases have a stronger bond than A&T bases. o More G&C bases in DNA means a higher melting point of DNA. Less G&C bases in DNA means a lower melting point of DNA. o The nucleotides of the four base pairs are linked together covalently by phosphodiester bonds. o The phosphodiester bonds join the 3’-hydroxyl(-OH) group of one sugar to the 5’-hydroxyl group of the next sugar. o A covalent bond is a stable chemical link between two atoms produced by sharing one or more pairs of electrons. o The DNA has a minor groove and major groove. Molecules are more likely to bind in the major groove, because there’s more room to bind there. The structure of DNA provides a mechanism for hereditary. One parental DNA double helix makes two new daughter DNA double helices. The S strand serves as a template for the new S’ strand, and the S’ strand serves as the template for the new S strand. This process is called semi-conservative replication. Genes contain the instructions for producing proteins. Gene A codes for protein A and gene B codes for protein B, etc. In eukaryotes, DNA is enclosed in a cell nucleus. Eukaryotic DNA is packaged into a set of chromosomes. They contain long strings of genes. The human chromosomes contain 23 pairs of chromosomes, so in total 46 chromosomes. In the binding patterns of human chromosomes, the horizontal red line represents the position of the centromere. The red knobs indicate the position of genes that code for large ribosomal RNAs. Human genes are much less densely packed, and the amount of interspersed DNA sequence is far greater compared to bacterial genes. The nucleotide sequence of the human genome shows how are genes are arranged. Exons code for a portion of the protein. Introns are relatively unimportant. Only 1.5% of DNA codes for exons. When an activating ligand is present, it activates the kinase, which results in kinase able to phosphorylate tyrosine to self-activate. This stimulates cell division. Nucleosomes are a basic unit of eukaryotic chromosome structure. The structural organisation of the nucleosome:

o o o o o

A nucleosome contains a protein core made of eight histone molecules. A histone is one of a group of small abundant proteins, rich in arginine and lysine. They combine to form the nucleosome cores around which the DNA is wrapped in eukaryotic chromosomes. Linker DNA is the red strings between the histone. The nucleosome core particle can be released from isolated chromatin by digestion of the linker DNA with a nuclease, which is an enzyme that breaks down DNA. The histone can be dissociated with a high concentration of salt.

The overall structural organisation of the core histones: A. Each of the core histones contains an N-terminal tail. B. The structure of the histone fold is formed by all four of the core histones. o The core of the histone has the interaction with the DNA. o The tails that stick out of the histone also stick out of the nucleosome and are making the nucleosomes a compact package. o There are eight tails, one tail from each histone protein that extend from each nucleosome. o There are different angles related to the different histone proteins. They might help to bend the chromosome around the nucleosome. o Sometimes the DNA has to be uncovered. o ATP is needed for the catalysis of nucleosome sliding. The structure of the nucleosome core particle reveals how DNA is packaged. The DNA helix makes 1.7 tight turns around the histone octamer. Nucleosomes have a dynamic structure and are frequently subjected to changes (nucleosome sliding) catalysed by ATP dependent chromatin remodelling complexes. By cooperating with specific members of a large family of different histone chaperones, some chromatin remodelling complexes can remove the H2A and H2B dimers from a nucleosome (top series of reactions on the picture) and replace them with dimers that contain a variant histone. Other remodelling complexes are attracted to specific sites on chromatin and cooperate with histone chaperones to remove the histone octamer completely and/or to replace it with a different nucleosome core (bottom series of reactions on the picture). Nucleosomes are usually packed together into a compact chromatin fiber.

Heterochromatin is highly organised and restricts gene expression. The heterochromatic state is selfpropagating. Heterochromatin are names of how DNA is being packaged. Heterochromatin is a very tightly bound part of the DNA. The White gene in the fruit fly controls eye pigment production and is named after the mutation that first identified it. Wild-type flies with a normal white gene (White+) have normal pigment production, which gives them red eyes. If the white gene is mutated and inactivated, the mutant flies (White- ) make no pigment and have white eyes. In flies in which a normal White gene has been moved near a region of heterochromatin, the eyes are mottled, with both red and white patches. The white patches represent cell lineages in which the White gene has been silenced by the effects of the heterochromatin. In contrast, the red patches represent cell lineages in which the White gene is expressed. Early in development, when the heterochromatin is first formed, it spreads into neighbouring euchromatin to different extends in different embryonic cells. The presence of large patches of red and white cells reveals that the state of transcriptional activity, as determined by the packaging of this gene in to chromatin in those ancestor cells, is inherited in all daughter cells. Heterochromatin (green in the picture) is normally prevented from spreading into adjacent regions of euchromatin (red in the picture) by barrier DNA sequences. In flies that inherit certain chromosomal regions, the barrier is no longer present. During the early development of such flies, heterochromatin can spread into neighbouring chromosomal DNA, proceeding for different distances in different cells. This spreading soon stops, but the established pattern of heterochromatin is subsequently inherited, so that large clones of progeny cells are produced that have the same neighbouring genes condensed into heterochromatin and thereby inactivated. This is what epigenetics do. Epi is the Greek word for on top, so on top of the normal genes. Euchromatin is a less condensed form of chromatin. The core histones are covalently modified at many different sites. The modification happens at the tales of the different histones. Covalent modifications and histone variants act in concert to control chromosome functions, so they work together. Some prominent types of covalent amino acid side-chain modifications found on nucleosomal histones. Three different levels of lysine methylation are shown in the picture. Each can be recognised by a different binding protein and thus each can have a different significance for the cell. Acetylation removes the plus charge on lysine, and most importantly, an acetylated lysine cannot be methylated, therefore lysine acetylation and methylation are competing reactions. Serine phosphorylation adds a negative charge to a histone.

The core of histone tails are covalently modificated in different ways. If there is a trimethyl at place nine, it will be packed in the heterochromatin and it will shut off. This means gene silencing. If there is a methyl group at place four and an acetyl group at place nine, it means gene expression. Some chromatin structures can be directly inherited, and movement of chromatin can be inherited as well. The heterochromatin pattern is copied and is given to the daughter cells in the body. This is why epigenetic modification is occurring in the body cells. It is not transferred to the sex cells, so this is not something that is handed over to the offspring. The picture on the right shows how the packaging of DNA in chromatin can be inherited following chromosome replication. Some of the specialised chromatin components are distributed to each sister chromosome after DNA duplication, along with the specially marked nucleosomes that they bind. After DNA replication, the inherited nucleosomes that are specially modified, acting in concert with the inherited chromatin components, change the pattern of histone modification on the newly formed nucleosomes nearby. This creates new binding sites for the same chromatin components, which then assemble to complete the structure. Epigenetics comes with ageing. That will determine how your histones are being modified. Diet and lifestyle influence this. The chromatin pattern you accumulate during life will depend on it. So, not only the genes play a role in developing diseases, also lifestyle and surroundings do. There is also switches that play a role in epigenetics and switching on or off the histone modification. Chromosomes are folded into large loops of chromatin. Mitotic chromosome are especially highly condensed. o A chromosome consists of two chromatids. o Each sister chromatid contains one of two identical sister DNA molecules, generated earlier in the cell cycle by DNA replication. o The centromere is the idle section of the two chromatids/of the chromosome. Chromatin packing: o Nucleosomes are packed together in the chromatin 1. Short region of DNA double helix. 2. ‘beads on a string’ form of chromatin. 3. Chromatin fiber of packed nucleosomes. 4. Chromatin fiber folded into loops. 5. Entire mitotic chromosome. o Each DNA molecule has been packaged into a mitotic chromosome that is 10.000-fold shorter that its fully extended length. People with the BRCA1 gen have a high chance of developing breast cancer. The breast cancer gene BRCA1 makes sick because the DNA is unravelled. The DNA should be tightly packed and not covered. This means that some genes are being expressed that should not be expressed. Heterochromatin mediated silencing BRCA1 tumour suppression occurs via heterochromatin mediated silencing. Ectopic expression of H2A fused to ubiquitin reverses the effects of BRCA1 loss, indicating that BRCA1 maintains the heterochromatin structure via ubiquitylation of histone H2A....