History of DNA research

Further information: History of molecular biology

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".^[117] In 1919 this discovery was followed by Phoebus Levene's identification of the base, sugar and phosphate nucleotide unit.^[118] Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.^[119]

In 1928, Frederick Griffith discovered that traits of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.^[120] This system provided the first clear suggestion that DNA carried genetic information, when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943.^[121] DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment showed that DNA is the genetic material of the T2 phage.^[122]

In 1953, based on X-ray diffraction images^[123] taken by Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick suggested^[123] what is now accepted as the first accurate model of DNA structure in the journal Nature.^[5] Experimental evidence for Watson and Crick's model were published in a series of five articles in the same issue of Nature.^[124] Of these, Franklin and Raymond Gosling's paper was the first publication of X-ray diffraction data that supported the Watson and Crick model,^[125][126] this issue also contained an article on DNA structure by Maurice Wilkins and his colleagues.^[127] In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.^[128] However, debate continues on who should receive credit for the discovery, as the Watson and Crick article in Nature was based on Franklin's data without either acknowledgment or her knowledge.^[129]

In an influential presentation in 1957, Crick laid out the "Central Dogma" of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".^[130] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment.^[131] Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code.^[132] These findings represent the birth of molecular biology.

http://en.wikipedia.org/wiki/DNA

DNA major and minor grooves

The double helix is a right-handed spiral. As the DNA strands wind around each other, they leave gaps between each set of phosphate backbones, revealing the sides of the bases inside (see animation). There are two of these grooves twisting around the surface of the double helix: one groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide.^[10] The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove.^[11]

Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. Large version<sup>[9]

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DNA

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of blueprints, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.

Chemically, DNA is a long polymer of simple units called nucleotides, with a backbone made of sugars and phosphate groups joined by ester bonds. Attached to each sugar is one of four types of molecules called bases. It is the sequence of these four bases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA, in a process called transcription.

Within cells, DNA is organized into structures called chromosomes. These chromosomes are duplicated before cells divide, in a process called DNA replication. Eukaryotic organisms (animals, plants, and fungi) store their DNA inside the cell nucleus, while in prokaryotes (bacteria and archae) it is found in the cell's cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

The structure of part of a DNA double helix


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Chromosome

Chromosomes are organized structures of DNA and proteins that are found in cells. Chromosomes contain a single continuous piece of DNA, which contains many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. The word chromosome comes from the Greek χρῶμα (chroma, color) and σῶμα (soma, body) due to their property of being stained very strongly by some dyes.

Chromosomes vary extensively between different organisms. The DNA molecule may be circular or linear, and can contain anything from tens of kilobase pairs to hundreds of megabase pairs. Typically eukaryotic cells (cells with nuclei) have large linear chromosomes and prokaryotic cells (cells without defined nuclei) have smaller circular chromosomes, although there are many exceptions to this rule. Furthermore, cells may contain more than one type of chromosome; for example mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosomes.

In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin. This allows the massively-long DNA molecules to fit into the cell nucleus. The structure of chromatin varies through the cell cycle, and is responsible for the organization of chromosomes into the classic four-arm structure during mitosis and meiosis.

"Chromosome" is a rather loosely defined term. In prokaryotes, a small circular DNA molecule may be called either a plasmid or a small chromosome. These small circular genomes are also found in mitochondria and chloroplasts, reflecting their bacterial origins. The simplest chromosomes are found in viruses: these DNA or RNA molecules are short linear or circular chromosomes that often lack any structural proteins.

A scheme of a condensed (metaphase) chromosome. (1) Chromatid - one of the two identical parts of the chromosome after S phase. (2) Centromere - the point where the two chromatids touch, and where the microtubules attach. (3) Short arm. (4) Long arm.

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