DNA

Deoxyribonucleic acid (DNA) is a nucleic acid molecule consisting of long chains of polymerized (deoxyribo) nucleotides. In double-stranded DNA the two strands are held together by hydrogen bonds between complementary nucleotide base pairs.
DNA was discovered in 1869 by Johann Friedrich Miescher, a Swiss biochemist working in Tubigen, Germany, The first extracts that Miescher made from human white blood cells were crude mixtures of DNA and chromosomal proteins. Next year he prepared a pure sample of nucleic acid from Salomon sperm, The chemical test showed that DNA is acidic and rich in phosphorus, and also suggested that the individual molecules are very large, although it was not until the 1930s when biophysical techniques are applied to DNA that huge lengths of polymeric chains were fully appreciated.



The basic building block of nucleic acids is the nucleotide. This has three components:

* a nitrogenous base;
* a sugar;
* and a phosphate.

The nitrogenous base is a purine or pyrimidine ring. The base is linked to position 1 on a pentose sugar by a glycosidic bond from N1 of pyrimidines or N9 of purines. To avoid ambiguity between the numbering systems of the heterocyclic rings and the sugar, positions on the pentose are given a prime ().

Nucleic acids are named for the type of sugar; DNA has 2–deoxyribose, whereas RNA has ribose. The difference is that the sugar in RNA has an OH group at the 2 position of the pentose ring. The sugar can be linked by its 5 or 3 position to a phosphate group.

A nucleic acid consists of a long chain of nucleotides. the backbone of the polynucleotide chain consists of an alternating series of pentose (sugar) and phosphate residues. This is constructed by linking the 5 position of one pentose ring to the 3 position of the next pentose ring via a phosphate group. So the sugar-phosphate backbone is said to consist of 5–3 phosphodiester linkages. The nitrogenous bases "stick out" from the backbone.

Each nucleic acid contains 4 types of base. The same two purines, adenine and guanine, are present in both DNA and RNA. The two pyrimidines in DNA are cytosine and thymine; in RNA uracil is found instead of thymine. The only difference between uracil and thymine is the presence of a methyl substituent at position C5. The bases are usually referred to by their initial letters. DNA contains A, G, C, T, while RNA contains A, G, C, U.
The terminal nucleotide at one end of the chain has a free 5 group; the terminal nucleotide at the other end has a free 3 group. It is conventional to write nucleic acid sequences in the 5→3 direction—that is, from the 5 terminus at the left to the 3 terminus at the right.

The replication process is initiated at particular points within the DNA, known as "origins", which are targeted by proteins that separate the two strands and initiate DNA synthesis.Origins contain DNA sequences recognized by replication initiator proteins (eg. dnaA in E coli' and the Origin Recognition Complex in yeast). These initiator proteins recruit other proteins to separate the two strands and initiate replication forks.

Initiator proteins recruit other proteins to separate the DNA strands at the origin, forming a bubble. Origins tend to be "AT-rich" (rich in adenine and thymine bases) to assist this process because A-T base pairs have two hydrogen bonds (rather than the three formed in a C-G pair)—strands rich in these nucleotides are generally easier to separate. Once strands are separated, RNA primers are created on the template strands and DNA polymerase extends these to create newly synthesized DNA.

As DNA synthesis continues, the original DNA strands continue to unwind on each side of the bubble, forming replication forks. In bacteria, which have a single origin of replication on their circular chromosome, this process eventually creates a "theta structure" (resembling the Greek letter theta: θ). In contrast, eukaryotes have longer linear chromosomes and initiate replication at multiple origins within these.

The replication fork

The replication fork is a structure which forms when DNA is being replicated. It is created through the action of helicase, which breaks the hydrogen bonds holding the two DNA strands together. The resulting structure has two branching "prongs", each one made up of a single strand of DNA.

Leading strand synthesis

In DNA replication, the leading strand is defined as the new DNA strand at the replication fork that is synthesized in the 5'→3' direction in a continuous manner. When the enzyme helicase unwinds DNA, two single stranded regions of DNA (the "replication fork") form. On the leading strand DNA polymerase III is able to synthesize DNA using the free 3' OH group donated by a single RNA primer and continuous synthesis occurs in the direction in which the replication fork is moving.

Lagging strand synthesis

The lagging strand is the DNA strand at the opposite side of the replication fork from the leading strand, running in the 3' to 5' direction. Because DNA polymerase cannot synthesize in the 3'→5' direction, the lagging strand is synthesized in short segments known as Okazaki fragments. Along the lagging strand's template, primase builds RNA primers in short bursts. DNA polymerases are then able to use the free 3' OH groups on the RNA primers to synthesize DNA in the 5'→3' direction. The RNA fragments are then removed (different mechanisms are used in eukaryotes and prokaryotes) and new deoxyribonucleotides are added to fill the gaps where the RNA was present. DNA ligase then joins the deoxyribonucleotides together, completing the synthesis of the lagging strand.















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Alu sequence

Alu sequence is a short stretch of DNA originally characterized by the action of the Alu restriction endonuclease. Alu sequences of different kinds occur in large numbers in primate genomes. In fact, Alu sequences are the most abundant mobile elements in the human genome. They are derived from the small cytoplasmic 7SL RNA, a component of the signal recognition particle. The event, when a copy of the 7SL RNA became a precursor of the Alu sequence, took place in the genome of an ancestor of Supraprimates.



Transcript


The bulk of human genome contains many sequence that do not code for any protein. These regions of genome are sometimes referred to as "junk" Dna,and make up more than 98% pf human genome.Included in the non-coding dna are many repetitive dna sequences. Two important families of repetitive elements are LINEs(Long Interspersed Elements) and the SINEs(Short Interspersed Elements).L1 is the most prevalent LINEs, and makes up about 17% of human genome.

Alu is the most prevalent SINEs,and equals about 11% of the genome,Alu and other SINEs are "defective" transposons;they depend on the enzymes of other transposons like L1,for mobility.It is estimated that there are about 75000 L1 and 1200000 Alu elements distributed throughout the human genome. Lets take a closer look at a single copy of each


L1 ,at approximately 20 times the length of Alu,encodes all the molecular machinery needed to replicate and move within the genome.An l1 element is approximately 6000 nucleotides in length, with two untranslated regions(UTRs)and two open reading frames(ORFs).

The ORF protein products assemble into complex that enables L1 and elements such as Alu to move throughout the genome.The structure of L1 is a stark contrast with that of the tiny 300 nucleotide Alu,Alu elements have no open reading frames and so encode no proteins.


Alu elements are characterized by a sequence with two G/C rich regions: the let(L-Alu) and the right(R-Alu) monomers. An A-rich linker connects these monomers. Alu elements end with a poly-A tail.In the genome, Alu elements are immediately flanked by A=T rich sequences.

The L-Alu regions contains two specific features Box A and Box B,which are binding sites of transcription factors and RNA polymerase III.Alu elements are transcribed into RNA by these proteins until they reach a stretch of T's is the genomic DNA.

The Alu Rna can act as template for the formation of a new Alu element that can itself in a new genome location. A likely model for this process requires the enzyme, a reverse transcriptase(rt),encoded by L1.

In addition to reverse transcription,L1 rt has teh unique ability to nick DNA in a site-preferential manner. Most ofen the nick is made at the consensus sequence TTAAA.This can create a single-stranded sequences of Ts that hydrogen bonds with the poly-A tail of the Alu RNA to form a short RNA/DNA heteroduplex.

The heteroduplex than can serve as a primer for L1 rt to synthesize a complementary (c) DNA strand.

A second nick is mode on the opposite strand, a variable distance from the initial cleavage site. Then, either the L1 rt or a cellular Dna polymerase synthesizes the second DNA strand.

This results in an Alu element inserted into a novel position of the genome. The insertion also creates a direct repeat sequence on either side of the element.

DNA

Deoxyribonucleic acid (DNA) is a nucleic acid molecule consisting of long chains of polymerized (deoxyribo) nucleotides. In double-stranded DNA the two strands are held together by hydrogen bonds between complementary nucleotide base pairs.
DNA was discovered in 1869 by Johann Friedrich Miescher, a Swiss biochemist working in Tubigen, Germany, The first extracts that Miescher made from human white blood cells were crude mixtures of DNA and chromosomal proteins. Next year he prepared a pure sample of nucleic acid from Salomon sperm, The chemical test showed that DNA is acidic and rich in phosphorus, and also suggested that the individual molecules are very large, although it was not until the 1930s when biophysical techniques are applied to DNA that huge lengths of polymeric chains were fully appreciated.












The basic building block of nucleic acids is the nucleotide. This has three components:
a nitrogenous base;
a sugar;
and a phosphate.
The nitrogenous base is a purine or pyrimidine ring. The base is linked to position 1 on a pentose sugar by a glycosidic bond from N1 of pyrimidines or N9 of purines. To avoid ambiguity between the numbering systems of the heterocyclic rings and the sugar, positions on the pentose are given a prime ().

Nucleic acids are named for the type of sugar; DNA has 2–deoxyribose, whereas RNA has ribose. The difference is that the sugar in RNA has an OH group at the 2 position of the pentose ring. The sugar can be linked by its 5 or 3 position to a phosphate group.

A nucleic acid consists of a long chain of nucleotides. the backbone of the polynucleotide chain consists of an alternating series of pentose (sugar) and phosphate residues. This is constructed by linking the 5 position of one pentose ring to the 3 position of the next pentose ring via a phosphate group. So the sugar-phosphate backbone is said to consist of 5–3 phosphodiester linkages. The nitrogenous bases "stick out" from the backbone.







Each nucleic acid contains 4 types of base. The same two purines, adenine and guanine, are present in both DNA and RNA. The two pyrimidines in DNA are cytosine and thymine; in RNA uracil is found instead of thymine. The only difference between uracil and thymine is the presence of a methyl substituent at position C5. The bases are usually referred to by their initial letters. DNA contains A, G, C, T, while RNA contains A, G, C, U.
The terminal nucleotide at one end of the chain has a free 5 group; the terminal nucleotide at the other end has a free 3 group. It is conventional to write nucleic acid sequences in the 5→3 direction—that is, from the 5 terminus at the left to the 3 terminus at the right.

The replication process is initiated at particular points within the DNA, known as "origins", which are targeted by proteins that separate the two strands and initiate DNA synthesis.Origins contain DNA sequences recognized by replication initiator proteins (eg. dnaA in E coli' and the Origin Recognition Complex in yeast). These initiator proteins recruit other proteins to separate the two strands and initiate replication forks.

Initiator proteins recruit other proteins to separate the DNA strands at the origin, forming a bubble. Origins tend to be "AT-rich" (rich in adenine and thymine bases) to assist this process because A-T base pairs have two hydrogen bonds (rather than the three formed in a C-G pair)—strands rich in these nucleotides are generally easier to separate. Once strands are separated, RNA primers are created on the template strands and DNA polymerase extends these to create newly synthesized DNA.

As DNA synthesis continues, the original DNA strands continue to unwind on each side of the bubble, forming replication forks. In bacteria, which have a single origin of replication on their circular chromosome, this process eventually creates a "theta structure" (resembling the Greek letter theta: θ). In contrast, eukaryotes have longer linear chromosomes and initiate replication at multiple origins within these.





The replication fork





The replication fork is a structure which forms when DNA is being replicated. It is created through the action of helicase, which breaks the hydrogen bonds holding the two DNA strands together. The resulting structure has two branching "prongs", each one made up of a single strand of DNA.






Leading strand synthesis






In DNA replication, the leading strand is defined as the new DNA strand at the replication fork that is synthesized in the 5'→3' direction in a continuous manner. When the enzyme helicase unwinds DNA, two single stranded regions of DNA (the "replication fork") form. On the leading strand DNA polymerase III is able to synthesize DNA using the free 3' OH group donated by a single RNA primer and continuous synthesis occurs in the direction in which the replication fork is moving.





Lagging strand synthesis






The lagging strand is the DNA strand at the opposite side of the replication fork from the leading strand, running in the 3' to 5' direction. Because DNA polymerase cannot synthesize in the 3'→5' direction, the lagging strand is synthesized in short segments known as Okazaki fragments. Along the lagging strand's template, primase builds RNA primers in short bursts. DNA polymerases are then able to use the free 3' OH groups on the RNA primers to synthesize DNA in the 5'→3' direction. The RNA fragments are then removed (different mechanisms are used in eukaryotes and prokaryotes) and new deoxyribonucleotides are added to fill the gaps where the RNA was present. DNA ligase then joins the deoxyribonucleotides together, completing the synthesis of the lagging strand.