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Human cells contain more than 6 billion base pairs of DNA, which would measure over 2 metersEven DNA in the smallest human chromosome would stretch 14,000 times the length of the nucleus.The primary structure of DNA is its nucleotide sequence; the secondary structure is the double-stranded helix; and the tertiary structure refers to higher-order foldingthat allows DNA to be packed into the confined space of a cell.Negativelysupercoiled DNA is underrotated; so separation of the two strands during replication and transcription is more rapid and requires less energy. Second, supercoiled DNA can bepacked into a smaller space than can relaxed DNA.

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The two basic types of chromatin are euchromatin,which undergoes the normal process of condensation and decondensation in the cell cycle, and heterochromatin, which remains in a highly condensed state throughout the cell cycle, even during interphase.

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Heterochromatin is also present at other specific places on some chromosomes, along the entire inactive X chromosome in female mammals and throughout most of the Y chromosome in males. In addition to remaining condensed throughout the cell cycle, heterochromatin is characterized by a general lack of transcription, the absence of crossing over, and replication late in the S stage.

All histones have a high percentage of arginine and lysine, positively charged amino acids that give the histones a net positive charge. The positive charges attract the negative charges on the phosphates of DNA; this attraction holds the DNA in contact with the histones. A heterogeneous assortment of nonhistone chromosomal proteins also are found in eukaryotic chromosomes.

.اسيد آمينه دارد) H1( ٢٠٠تا ) H4( ١٠٠هر هيستون حدود

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Each of the histone proteins has a flexible (N-terminal) tail, containing from 11 to 37 amino acids, that extends out from the nucleosome. Positively charged amino acids in the tails of the histones interact with the negative charges of the phosphates on the DNA, keeping the DNA and histones tightly associated.

The tails may also interact with neighboring nucleosomes, which facilitates compaction of the nucleosomes themselves. Chemical modifications of the histone tails bring about changes in chromatin structure that are necessary for gene expression.

The fifth type of histone, H1, is not a part of the ore particle but plays an important role in nucleosome structure. H1 binds to 20 to 22 bp of DNA where the DNA joins and leaves the octamer (see Figure 11.4) and helps to lock the DNA into place, acting as a clamp around the nucleosome octamer.

Together, the core particle and its associated H1 histone are called the chromatosome (see Figure 11.4), the next level of chromatin organization. Each chromatosome encompasses about 167 bp of DNA.

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TRANSDUCTION The exchange of genetic material from one cell to another that is mediated by a virus or phage.TRANSFORMATION The uptake of DNA by a bacterium from the surrounding environment.CONJUGATION In prokaryotes, the transfer of DNA from a donor cell to a recipient cell that is mediated by direct cell–cell contact.

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When genes become transcriptionally active, they also become sensitive to Dnase I, indicating that the chromatin structure is more exposed during transcription.In this case, the histones loosen their grip on the DNA.

One process that alters chromatin structure is acetylation. Enzymes called acetyltransferases attach acetyl groups to lysine amino acids on the histone tails. This modification reduces the positive charges that normally exist on lysine and destabilizes the nucleosome structure, and so the histones hold the DNA less tightly.

Other chemical modifications of the histone proteins, such as methylation and phosphorylation, also alter chromatin structure, as do special chromatin-remodeling proteins that bind to the DNA.

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Some chemical modification to chromatin structure are retained through cell division, and so they are passed on future generations of cells and even occasionally to future generations of organisms.

Genomic imprinting is caused by differences in DNA and some histone proteins methylation patterns between male and female gamete. These gametes are differentially methylated at various imprinting control regions during gmete formation, and the different methylation patterns of paternal and maternal alleles are then maintained and passed on to all resulting cells in the zygote.

Interestingly, demethylation of some histones is required before methylation of imprinting control regions in the DNA can take place.

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The first clue that eukaryotic DNA contains several types of sequences not present in prokaryotic DNA came from studies in which double-stranded DNA was separated andthen allowed to reassociate. When double-stranded DNA in solution is heated, the hydrogen bonds that hold the two strands together are weakened and, with enough heat, the two nucleotide strands separate completely (a process called denaturation or melting). The temperature at which DNA denatures, called the melting temperature (Tm). CG or AT

If single-stranded DNA is slowly cooled, single strands complementary base pairs, producing double-stranded DNA. (renaturation or reannealing).

Two complementary ssDNA from different sources, such as different organisms, will anneal (hybridization). For hybridization, the two strands do not have to be complementary at all their bases—just at enough bases to hold the two strands together.

The extent of hybridization can be used to measure the similarity of nucleic acids from two different sources and is a common tool for assessing evolutionary relationships.

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Unique-sequence DNA consists of sequences that are present only once or, at most, a few times in the genome. This DNA includes sequences that encode proteins, as well as a great deal of DNA whose function is unknown.

Some eukaryots have large amounts of repetitive DNA; half of the human genome consists of repetitive DNA. moderately repetitive DNA, typically consists of sequences from 100 to 1000 bp that are repeated many thousands of times.Some of these sequences are important for example, rRNAs and tRNAs.

highly repetitive DNA are present in hundreds of thousands copies that are repeated in tandem (in the blocks of less than 100 bp to 30 kb) and clustered in certain regions of the chromosome, especially at centromeres and telomeres. (حتی درون ژنها نيز وجود دارند)

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flanking direct repeats from 3 to 12 bp long are present on both sides of most transposable elements. They are not a part of a transposable element and do not travel with it. Rather, they are generated in the process of transposition, at the point of insertion.

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Most transposons found in bacteria are DNA transposons. Both type are found in eukaryotes, although retrotransposons are more common.

Among DNA transpsons, transposition may be replicative (copy-and-paste transpostion) ornonreplicative transposition (cut-and-paste transposition).

Retrotransposons use replicative transposition only.

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In the steps of transposition between two circular DNA molecules: The transposable element is replicated, producing the cointegrate structure that consists of molecules A + B fused together with two copies of the transposable element.

First, a transposase enzyme (often encoded by the transposable element) makes single-strand breaks at each end and on either side of the target sequence. Second, the free ends of the transposable element attach to the free ends of the target sequence. Third, replication takes place on the single-strand templates, beginning at the 3′ ends of the single strands and proceeding through the transposable element.

the cointegrate undergoes resolution, which requires crossing over inside the transposon. Resolution gives rise to two copies of the transposable element. The resolution step is brought about by resolvase enzymes (encoded in some cases by the transposable element and in other cases by a cellular gene.

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A common method of repair is to remove and then replicate the broken segment of DNA using the homologous template on the sister chromatid. Before transposition, both sister chromatids have a copy of the transposable element. After transposition (in which the transposable element moves to a new site) and repair of the break (which restores the original copy), the number of copies of the transposable element will have increased by one.

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50% of mutations in Drosophila result from transposons in or near a functional gene.

Although most mutations resulting from transposition are detrimental, they may activate a gene or change the phenotype in a beneficial way. For instance, bacterial transposable elements sometimes carry genes that encode antibiotic resistance, and some transposons have created mutations that confer insecticide resistance in insects.

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White grapes resulted from a mutation in black grapes that turned off the production of anthocyanin pigments. This mutation consisted of the insertion of a 10,422- bp retrotransposon called Gret1 near a gene that

red grapes resulted from a second mutation in the white grapes. This mutation (probably resulting from faulty recombination) removed most but not all of the retrotransposon, switching pigment production backpromotes the production of anthocyanins.

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DNA rearrangements can also be caused by transposons in a cut-and-paste transposition. If the broken DNA is not repaired properly, a chromosome rearrangement can be generated. This type of chromosome breakage led to the discovery of transposable elements. She named the gene that appeared at these sites Dissociation, because of the tendency for it to cause chromosome breakage and the loss of a fragment.

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Mny replicative transposons increase in number with each transposition. In the absence of mechanisms to restrict transposition, the number of copies of transposable elements would increase continuously (high rate of mutation).

DNA methylation usually suppresses transcription preventing the production of the transposase enzyme necessary for transposition.

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** Geneticists designate each type of insertion sequence with IS followed by a number. For example IS1 is a common IS in E. coli.

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IS at the ends of a composite transposon are responsible for transposition. The DNA between the ISs is not required for movement and may carry additional information such as antibiotic resistance.

The composite transposon Tn10, for example, is about 9 kb and carries a gene for tetracycline resistance between two IS10 insertion sequences.

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Example for Noncomposite transposones: The noncomposite transposon Tn3 carries genes for transposase and resolvase plus a gene that encodes the enzyme β-lactamase, which provides resistance to the antibiotic ampicillin.

A few bacteriophage genomes reproduce by transposition and use transposition to insert themselves into a bacterial chromosome in their lysogenic cycle (such as bacteriophages Mu). Although Mu does not possess terminal inverted repeats, it does generate short (5-bp) flanking direct repeats when it inserts into DNA. Mu replicates through transposition and causes mutations at the site of insertion, properties characteristic of transposable elements.

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Retrotransposons; use RNA intermediates, and are similar in structure and movement to retroviruses.

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Ty elements in yeast Ty elements are a family retrotransposon in yeast; many yeast cells have 30 copies of Ty elements.

Delta sequences: Analogous to the long terminal repeats found in retroviruses and contain several genes that are related to the gag and pol genes present in retroviruses. The delta sequences also contain promoters required for the transcription of Ty genes, and the promoters can also stimulate the transcription of genes that lie downstream of the Ty element.

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