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Biologists in the 1940s had difficulty in accepting DNA as the genetic material because of the apparent simplicity of its chemistry. DNA was known to be a long polymer composed of only four types of subunits, which resemble one another chemically. Early in the 1950s, DNA was first examined by x-ray diffraction analysis, a technique for determining the three-dimensional atomic structure of a molecule (discussed in Chapter 8). The early x-ray diffraction results indicated that DNA was composed of two strands of the polymer wound into a helix. The observation that DNA was double-stranded was of crucial significance and provided one of the major clues that led to the Watson-Crick structure of DNA. Only when this model was proposed did DNA's potential for replication and information encoding become apparent. In this section we examine the structure of the DNA molecule and explain in general terms how it is able to store hereditary information.

A DNA molecule consists of two long polynucleotide chains composed of four types of nucleotide subunits. Each of these chains is known as a DNA chain, or a DNA strand. Hydrogen bonds between the base portions of the nucleotides hold the two chains together (). As we saw in Chapter 2 (Panel 2-6, pp. 120-121), nucleotides are composed of a five-carbon sugar to which are attached one or more phosphate groups and a nitrogen-containing base. In the case of the nucleotides in DNA, the sugar is deoxyribose attached to a single phosphate group (hence the name deoxyribonucleic acid), and the base may be either adenine (A), cytosine (C), guanine (G), or thymine (T). The nucleotides are covalently linked together in a chain through the sugars and phosphates, which thus form a backbone of alternating sugar-phosphate-sugar-phosphate (see ). Because only the base differs in each of the four types of subunits, each polynucleotide chain in DNA is analogous to a necklace (the backbone) strung with four types of beads (the four bases A, C, G, and T). These same symbols (A, C, G, and T) are also commonly used to denote the four different nucleotidesthat is, the bases with their attached sugar and phosphate groups.

DNA and its building blocks. DNA is made of four types of nucleotides, which are linked covalently into a polynucleotide chain (a DNA strand) with a sugar-phosphate backbone from which the bases (A, C, G, and T) extend. A DNA molecule is composed of two (more...)

The way in which the nucleotide subunits are lined together gives a DNA strand a chemical polarity. If we think of each sugar as a block with a protruding knob (the 5 phosphate) on one side and a hole (the 3 hydroxyl) on the other (see ), each completed chain, formed by interlocking knobs with holes, will have all of its subunits lined up in the same orientation. Moreover, the two ends of the chain will be easily distinguishable, as one has a hole (the 3 hydroxyl) and the other a knob (the 5 phosphate) at its terminus. This polarity in a DNA chain is indicated by referring to one end as the 3 end and the other as the 5 end.

The three-dimensional structure of DNAthe double helixarises from the chemical and structural features of its two polynucleotide chains. Because these two chains are held together by hydrogen bonding between the bases on the different strands, all the bases are on the inside of the double helix, and the sugar-phosphate backbones are on the outside (see ). In each case, a bulkier two-ring base (a purine; see Panel 2-6, pp. 120121) is paired with a single-ring base (a pyrimidine); A always pairs with T, and G with C (). This complementary base-pairing enables the base pairs to be packed in the energetically most favorable arrangement in the interior of the double helix. In this arrangement, each base pair is of similar width, thus holding the sugar-phosphate backbones an equal distance apart along the DNA molecule. To maximize the efficiency of base-pair packing, the two sugar-phosphate backbones wind around each other to form a double helix, with one complete turn every ten base pairs ().

Complementary base pairs in the DNA double helix. The shapes and chemical structure of the bases allow hydrogen bonds to form efficiently only between A and T and between G and C, where atoms that are able to form hydrogen bonds (see Panel 2-3, pp. 114115) (more...)

The DNA double helix. (A) A space-filling model of 1.5 turns of the DNA double helix. Each turn of DNA is made up of 10.4 nucleotide pairs and the center-to-center distance between adjacent nucleotide pairs is 3.4 nm. The coiling of the two strands around (more...)

The members of each base pair can fit together within the double helix only if the two strands of the helix are antiparallelthat is, only if the polarity of one strand is oriented opposite to that of the other strand (see and ). A consequence of these base-pairing requirements is that each strand of a DNA molecule contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand.

Genes carry biological information that must be copied accurately for transmission to the next generation each time a cell divides to form two daughter cells. Two central biological questions arise from these requirements: how can the information for specifying an organism be carried in chemical form, and how is it accurately copied? The discovery of the structure of the DNA double helix was a landmark in twentieth-century biology because it immediately suggested answers to both questions, thereby resolving at the molecular level the problem of heredity. We discuss briefly the answers to these questions in this section, and we shall examine them in more detail in subsequent chapters.

DNA encodes information through the order, or sequence, of the nucleotides along each strand. Each baseA, C, T, or Gcan be considered as a letter in a four-letter alphabet that spells out biological messages in the chemical structure of the DNA. As we saw in Chapter 1, organisms differ from one another because their respective DNA molecules have different nucleotide sequences and, consequently, carry different biological messages. But how is the nucleotide alphabet used to make messages, and what do they spell out?

As discussed above, it was known well before the structure of DNA was determined that genes contain the instructions for producing proteins. The DNA messages must therefore somehow encode proteins (). This relationship immediately makes the problem easier to understand, because of the chemical character of proteins. As discussed in Chapter 3, the properties of a protein, which are responsible for its biological function, are determined by its three-dimensional structure, and its structure is determined in turn by the linear sequence of the amino acids of which it is composed. The linear sequence of nucleotides in a gene must therefore somehow spell out the linear sequence of amino acids in a protein. The exact correspondence between the four-letter nucleotide alphabet of DNA and the twenty-letter amino acid alphabet of proteinsthe genetic codeis not obvious from the DNA structure, and it took over a decade after the discovery of the double helix before it was worked out. In Chapter 6 we describe this code in detail in the course of elaborating the process, known as gene expression, through which a cell translates the nucleotide sequence of a gene into the amino acid sequence of a protein.

The relationship between genetic information carried in DNA and proteins.

The complete set of information in an organism's DNA is called its genome, and it carries the information for all the proteins the organism will ever synthesize. (The term genome is also used to describe the DNA that carries this information.) The amount of information contained in genomes is staggering: for example, a typical human cell contains 2 meters of DNA. Written out in the four-letter nucleotide alphabet, the nucleotide sequence of a very small human gene occupies a quarter of a page of text (), while the complete sequence of nucleotides in the human genome would fill more than a thousand books the size of this one. In addition to other critical information, it carries the instructions for about 30,000 distinct proteins.

The nucleotide sequence of the human -globin gene. This gene carries the information for the amino acid sequence of one of the two types of subunits of the hemoglobin molecule, which carries oxygen in the blood. A different gene, the -globin (more...)

At each cell division, the cell must copy its genome to pass it to both daughter cells. The discovery of the structure of DNA also revealed the principle that makes this copying possible: because each strand of DNA contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand, each strand can act as a template, or mold, for the synthesis of a new complementary strand. In other words, if we designate the two DNA strands as S and S, strand S can serve as a template for making a new strand S, while strand S can serve as a template for making a new strand S (). Thus, the genetic information in DNA can be accurately copied by the beautifully simple process in which strand S separates from strand S, and each separated strand then serves as a template for the production of a new complementary partner strand that is identical to its former partner.

DNA as a template for its own duplication. As the nucleotide A successfully pairs only with T, and G with C, each strand of DNA can specify the sequence of nucleotides in its complementary strand. In this way, double-helical DNA can be copied precisely. (more...)

The ability of each strand of a DNA molecule to act as a template for producing a complementary strand enables a cell to copy, or replicate, its genes before passing them on to its descendants. In the next chapter we describe the elegant machinery the cell uses to perform this enormous task.

Nearly all the DNA in a eucaryotic cell is sequestered in a nucleus, which occupies about 10% of the total cell volume. This compartment is delimited by a nuclear envelope formed by two concentric lipid bilayer membranes that are punctured at intervals by large nuclear pores, which transport molecules between the nucleus and the cytosol. The nuclear envelope is directly connected to the extensive membranes of the endoplasmic reticulum. It is mechanically supported by two networks of intermediate filaments: one, called the nuclear lamina, forms a thin sheetlike meshwork inside the nucleus, just beneath the inner nuclear membrane; the other surrounds the outer nuclear membrane and is less regularly organized ().

A cross-sectional view of a typical cell nucleus. The nuclear envelope consists of two membranes, the outer one being continuous with the endoplasmic reticulum membrane (see also Figure 12-9). The space inside the endoplasmic reticulum (the ER lumen) (more...)

The nuclear envelope allows the many proteins that act on DNA to be concentrated where they are needed in the cell, and, as we see in subsequent chapters, it also keeps nuclear and cytosolic enzymes separate, a feature that is crucial for the proper functioning of eucaryotic cells. Compartmentalization, of which the nucleus is an example, is an important principle of biology; it serves to establish an environment in which biochemical reactions are facilitated by the high concentration of both substrates and the enzymes that act on them.

Genetic information is carried in the linear sequence of nucleotides in DNA. Each molecule of DNA is a double helix formed from two complementary strands of nucleotides held together by hydrogen bonds between G-C and A-T base pairs. Duplication of the genetic information occurs by the use of one DNA strand as a template for formation of a complementary strand. The genetic information stored in an organism's DNA contains the instructions for all the proteins the organism will ever synthesize. In eucaryotes, DNA is contained in the cell nucleus.

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The Structure and Function of DNA - Molecular Biology of the ...

DNA - STRUCTURE

This page, looking at the structure of DNA, is the first in a sequence of pages leading on to how DNA replicates (makes copies of) itself, and then to how information stored in DNA is used to make protein molecules. This material is aimed at 16 - 18 year old chemistry students. If you are interested in this from a biological or biochemical point of view, you may find these pages a useful introduction before you get more information somewhere else.

Chemistry students at UK A level (or its various equivalents) should not waste time on this. The booklet is written for A level biology students, and goes into far more detail than you will need for chemistry purposes.

A quick look at the whole structure of DNA

These days, most people know about DNA as a complex molecule which carries the genetic code. Most will also have heard of the famous double helix.

I'm going to start with a diagram of the whole structure, and then take it apart to see how it all fits together. The diagram shows a tiny bit of a DNA double helix.

Normally I prefer to draw my own diagrams, but my drawing software isn't sophisticated enough to produce convincing twisted "ribbons".

Exploring a DNA chain

The sugars in the backbone

The backbone of DNA is based on a repeated pattern of a sugar group and a phosphate group. The full name of DNA, deoxyribonucleic acid, gives you the name of the sugar present - deoxyribose.

Deoxyribose is a modified form of another sugar called ribose. I'm going to give you the structure of that first, because you will need it later anyway. Ribose is the sugar in the backbone of RNA, ribonucleic acid.

This diagram misses out the carbon atoms in the ring for clarity. Each of the four corners where there isn't an atom shown has a carbon atom.

The heavier lines are coming out of the screen or paper towards you. In other words, you are looking at the molecule from a bit above the plane of the ring.

So that's ribose. Deoxyribose, as the name might suggest, is ribose which has lost an oxygen atom - "de-oxy".

The only other thing you need to know about deoxyribose (or ribose, for that matter) is how the carbon atoms in the ring are numbered.

The carbon atom to the right of the oxygen as we have drawn the ring is given the number 1, and then you work around to the carbon on the CH2OH side group which is number 5.

You will notice that each of the numbers has a small dash by it - 3' or 5', for example. If you just had ribose or deoxyribose on its own, that wouldn't be necessary, but in DNA and RNA these sugars are attached to other ring compounds. The carbons in the sugars are given the little dashes so that they can be distinguished from any numbers given to atoms in the other rings.

You read 3' or 5' as "3-prime" or "5-prime".

Attaching a phosphate group

The other repeating part of the DNA backbone is a phosphate group. A phosphate group is attached to the sugar molecule in place of the -OH group on the 5' carbon.

I don't want to get bogged down in this. The version I am using is fine for chemistry purposes, and will make it easy to see how the DNA backbone is put together. We are soon going to simplify all this down anyway!

Attaching a base and making a nucleotide

The final piece that we need to add to this structure before we can build a DNA strand is one of four complicated organic bases. In DNA, these bases are cytosine (C), thymine (T), adenine (A) and guanine (G).

These bases attach in place of the -OH group on the 1' carbon atom in the sugar ring.

What we have produced is known as a nucleotide.

We now need a quick look at the four bases. If you need these in a chemistry exam at this level, the structures will almost certainly be given to you.

Here are their structures:

The nitrogen and hydrogen atoms shown in blue on each molecule show where these molecules join on to the deoxyribose. In each case, the hydrogen is lost together with the -OH group on the 1' carbon atom of the sugar. This is a condensation reaction - two molecules joining together with the loss of a small one (not necessarily water).

For example, here is what the nucleotide containing cytosine would look like:

Joining the nucleotides into a DNA strand

A DNA strand is simply a string of nucleotides joined together. I can show how this happens perfectly well by going back to a simpler diagram and not worrying about the structure of the bases.

The phosphate group on one nucleotide links to the 3' carbon atom on the sugar of another one. In the process, a molecule of water is lost - another condensation reaction.

. . . and you can continue to add more nucleotides in the same way to build up the DNA chain.

Now we can simplify all this down to the bare essentials!

Both are right and, equally, both are misleading! The shape of the bonds around the phosphorus atom is tetrahedral, and all of the bonds are at approximately 109 to each other. Whichever way you choose to draw this in 2-dimensions on paper, it still represents the same molecule in reality.

To take a simpler example, if you draw a structural formula for CH2Cl2 using simple bond notation, you could equally well draw the chlorine atoms at right angles to each other or opposite each other. The molecule would still be exactly the same. This is one of the things you had to learn when you first started drawing structures for organic molecules. If you still aren't sure about this, look again at the page about drawing organic molecules.

Building a DNA chain concentrating on the essentials

What matters in DNA is the sequence the four bases take up in the chain. We aren't particularly interested in the backbone, so we can simplify that down. For the moment, we can simplify the precise structures of the bases as well.

We can build the chain based on this fairly obvious simplification:

There is only one possible point of confusion here - and that relates to how the phosphate group, P, is attached to the sugar ring. Notice that it is joined via two lines with an angle between them.

By convention, if you draw lines like this, there is a carbon atom where these two lines join. That is the carbon atom in the CH2 group if you refer back to a previous diagram. If you had tried to attach the phosphate to the ring by a single straight line, that CH2 group would have got lost!

Joining up lots of these gives you a part of a DNA chain. The diagram below is a bit from the middle of a chain. Notice that the individual bases have been identified by the first letters of the base names. (A = adenine, etc). Notice also that there are two different sizes of base. Adenine and guanine are bigger because they both have two rings. Cytosine and thymine only have one ring each.

If the top of this segment was the end of the chain, then the phosphate group would have an -OH group attached to the spare bond rather than another sugar ring.

Similarly, if the bottom of this segment of chain was the end, then the spare bond at the bottom would also be to an -OH group on the deoxyribose ring.

Joining the two DNA chains together

The importance of "base pairs"

Have another look at the diagram we started from:

If you look at this carefully, you will see that an adenine on one chain is always paired with a thymine on the second chain. And a guanine on one chain is always paired with a cytosine on the other one.

So how exactly does this work?

The first thing to notice is that a smaller base is always paired with a bigger one. The effect of this is to keep the two chains at a fixed distance from each other all the way along.

But, more than this, the pairing has to be exactly . . .

That is because these particular pairs fit exactly to form very effective hydrogen bonds with each other. It is these hydrogen bonds which hold the two chains together.

The base pairs fit together as follows.

The A-T base pair:

The G-C base pair:

If you try any other combination of base pairs, they won't fit!

If hydrogen bonding worries you, follow this link for detailed explanations. Use the BACK button on your browser to return here later.

A final structure for DNA showing the important bits

Notice that the two chains run in opposite directions, and the right-hand chain is essentially upside-down. You will also notice that I have labelled the ends of these bits of chain with 3' and 5'.

If you followed the left-hand chain to its very end at the top, you would have a phosphate group attached to the 5' carbon in the deoxyribose ring. If you followed it all the way to the other end, you would have an -OH group attached to the 3' carbon.

In the second chain, the top end has a 3' carbon, and the bottom end a 5'.

This 5' and 3' notation becomes important when we start talking about the genetic code and genes. The genetic code in genes is always written in the 5' to 3' direction along a chain.

It is also important when we take a very simplified look at how DNA makes copies of itself on the next page . . .

To the next page about DNA . . .

To the amino acid and other biochemistry menu . . .

To the menu of other organic compounds . . .

To Main Menu . . .

Jim Clark 2007 (modified May 2016)

Originally posted here:
DNA - structure - chemguide

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DNA - Definition by AcronymFinder

People have known for many years that living things inherit traits from their parents. That common-sense observation led to agriculture, the purposeful breeding and cultivation of animals and plants for desirable characteristics. Firming up the details took quite some time, though. Researchers did not understand exactly how traits were passed to the next generation until the middle of the 20th century.

Now it is clear that genes are what carry our traits through generations and that genes are made of deoxyribonucleic acid (DNA). But genes themselves don't do the actual work. Rather, they serve as instruction books for making functional molecules such as ribonucleic acid (RNA) and proteins, which perform the chemical reactions in our bodies.

Proteins do many other things, too. They provide the body's main building materials, forming the cell's architecture and structural components. But one thing proteins can't do is make copies of themselves. When a cell needs more proteins, it uses the manufacturing instructions coded in DNA.

The DNA code of a genethe sequence of its individual DNA building blocks, labeled A (adenine), T (thymine), C (cytosine) and G (guanine) and collectively called nucleotides spells out the exact order of a protein's building blocks, amino acids.

Occasionally, there is a kind of typographical error in a gene's DNA sequence. This mistake which can be a change, gap or duplicationis called a mutation.

A mutation can cause a gene to encode a protein that works incorrectly or that doesn't work at all. Sometimes, the error means that no protein is made.

But not all DNA changes are harmful. Some mutations have no effect, and others produce new versions of proteins that may give a survival advantage to the organisms that have them. Over time, mutations supply the raw material from which new life forms evolve (see Chapter 3, "Life's Genetic Tree").

The monk Gregor Mendel first described how traits are inherited from one generation to the next.

In 1900, three European scientists independently discovered an obscure research paper that had been published nearly 35 years before. Written by Gregor Mendel, an Austrian monk who was also a scientist, the report described a series of breeding experiments performed with pea plants growing in his abbey garden.

Mendel had studied how pea plants inherited the two variant forms of easy-to-see traits. These included flower color (white or purple) and the texture of the peas (smooth or wrinkled). Mendel counted many generations of pea plant offspring and learned that these characteristics were passed on to the next generation in orderly, predictable ratios.

When he cross-bred purple-flowered pea plants with white-flowered ones, the next generation had only purple flowers. But directions for making white flowers were hidden somewhere in the peas of that generation, because when those purple-flowered plants were bred to each other, some of their offspring had white flowers. What's more, the second-generation plants displayed the colors in a predictable pattern. On average, 75 percent of the second-generation plants had purple flowers and 25 percent of the plants had white flowers. Those same ratios persisted, and were reproduced when the experiment was repeated many times over.

Trying to solve the mystery of the missing color blooms, Mendel imagined that the reproductive cells of his pea plants might contain discrete "factors," each of which specified a particular trait, such as white flowers. Mendel reasoned that the factors, whatever they were, must be physical material because they passed from parent to offspring in a mathematically orderly way. It wasn't until many years later, when the other scientists unearthed Mendel's report, that the factors were named genes.

Early geneticists quickly discovered that Mendel's mathematical rules of inheritance applied not just to peas, but also to all plants, animals and people. The discovery of a quantitative rule for inheritance was momentous. It revealed that a common, general principle governed the growth and development of all life on Earth.

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Up until the 1950s, scientists knew a good deal about heredity, but they didn't have a clue what DNA looked like. In order to learn more about DNA and its structure, some scientists experimented with using X rays as a form of molecular photography.

In 1953, Watson and Crick created their historic model of the shape of DNA: the double helix. COLD SPRING HARBOR LABORATORY ARCHIVES

Rosalind Franklin, a physical chemist working with Maurice Wilkins at King's College in London, was among the first to use this method to analyze genetic material. Her experiments produced what were referred to at the time as "the most beautiful X-ray photographs of any substance ever taken."

Other scientists, including zoologist James Watson and physicist Francis Crick, both working at Cambridge University in the United Kingdom, were trying to determine the shape of DNA too. Ultimately, this line of research revealed one of the most profound scientific discoveries of the 20th century: that DNA exists as a double helix.

The 1962 Nobel Prize in physiology or medicine was awarded to Watson, Crick and Wilkins for this work. Although Franklin did not earn a share of the prize due to her untimely death at age 38, she is widely recognized as having played a significant role in the discovery.

Rosalind Franklin's original X-ray diffraction photo revealed the physical structure of DNA. OREGON STATE UNIVERSITY LIBRARIES SPECIAL COLLECTIONS

The spiral staircase-shaped double helix has attained global status as the symbol for DNA. But what is so beautiful about the discovery of the twisting ladder structure isn't just its good looks. Rather, the structure of DNA taught researchers a fundamental lesson about genetics. It taught them that the two connected strandswinding together like parallel handrailswere complementary to each other, and this unlocked the secret of how genetic information is stored, transferred and copied.

In genetics, complementary means that if you know the sequence of nucleotide building blocks on one strand, you know the sequence of nucleotide building blocks on the other strand: A always matches up with T and C always links to G (see drawing).

Long strings of nucleotides form genes, and groups of genes are packaged tightly into structures called chromosomes. Every cell in your body except for eggs, sperm and red blood cells contains a full set of chromosomes in its nucleus.

If the chromosomes in one of your cells were uncoiled and placed end to end, the DNA would be about 6 feet long. If all the DNA in your body were connected in this way, it would stretch approximately 67 billion miles! That's nearly 150,000 round trips to the Moon.

The long, stringy DNA that makes up genes is spooled within chromosomes inside the nucleus of a cell. (Note that a gene would actually be a much longer stretch of DNA than what is shown here.)

DNA consists of two long, twisted chains made up of nucleotides. Each nucleotide contains one base, one phosphate molecule and the sugar molecule deoxyribose. The bases in DNA nucleotides are adenine, thymine, cytosine and guanine.

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Humans have 23 pairs of chromosomes. Male DNA (pictured here) contains an X and a Y chromosome, whereas female DNA contains two X chromosomes. CYTOGENETICS LABORATORY, BRIGHAM AND WOMEN'S HOSPITAL

It's astounding to think that your body consists of trillions of cells. But what's most amazing is that it all starts with one cell. How does this massive expansion take place?

As an embryo progresses through development, its cells must reproduce. But before a cell divides into two new, nearly identical cells, it must copy its DNA so there will be a complete set of genes to pass on to each of the new cells.

To make a copy of itself, the twisted, compacted double helix of DNA has to unwind and separate its two strands. Each strand becomes a pattern, or template, for making a new strand, so the two new DNA molecules have one new strand and one old strand.

The copy is courtesy of a cellular protein machine called DNA polymerase, which reads the template DNA strand and stitches together the complementary new strand. The process, called replication, is astonishingly fast and accurate, although occasional mistakes, such as deletions or duplications, occur. Fortunately, a cellular spell-checker catches and corrects nearly all of these errors.

When DNA polymerase makes an error while copying a gene's DNA sequence, the mistake is called a mutation. In this example, the nucleotide G has been changed to an A.

During DNA replication, each strand of the original molecule acts as a template for the synthesis of a new, complementary DNA strand.

Mistakes that are not corrected can lead to diseases such as cancer and certain genetic disorders. Some of these include Fanconi anemia, early aging diseases and other conditions in which people are extremely sensitive to sunlight and some chemicals.

DNA copying is not the only time when DNA damage can happen. Prolonged, unprotected sun exposure can cause DNA changes that lead to skin cancer, and toxins in cigarette smoke can cause lung cancer.

It may seem ironic, then, that many drugs used to treat cancer work by attacking DNA. That's because these chemotherapy drugs disrupt the DNA copying process, which goes on much faster in rapidly dividing cancer cells than in other cells of the body. The trouble is that most of these drugs do affect normal cells that grow and divide frequently, such as cells of the immune system and hair cells.

Understanding DNA replication better could be a key to limiting a drug's action to cancer cells only.

After copying its DNA, a cell's next challenge is getting just the right amount of genetic material into each of its two offspring.

Most of your cells are called diploid ("di" means two, and "ploid" refers to sets of chromosomes) because they have two sets of chromosomes (23 pairs). Eggs and sperm are different; these are known as haploid cells. Each haploid cell has only one set of 23 chromosomes so that at fertilization the math will work out: A haploid egg cell will combine with a haploid sperm cell to form a diploid cell with the right number of chromosomes: 46.

Chromosomes are numbered 1 to 22, according to size, with 1 being the largest chromosome. The 23rd pair, known as the sex chromosomes, are called X and Y. In humans, abnormalities of chromosome number usually occur during meiosis, the time when a cell reduces its chromosomes from diploid to haploid in creating eggs or sperm.

What happens if an egg or a sperm cell gets the wrong number of chromosomes, and how often does this happen?

Trisomy, the hallmark of Down syndrome, results when a baby is born with three copies of chromosome 21 instead of the usual two.

Molecular biologist Angelika Amon of the Massachusetts Institute of Technology in Cambridge says that mistakes in dividing DNA between daughter cells during meiosis are the leading cause of human birth defects and miscarriages. Current estimates are that 10 percent of all embryos have an incorrect chromosome number. Most of these don't go to full term and are miscarried.

In women, the likelihood that chromosomes won't be apportioned properly increases with age. One of every 18 babies born to women over 45 has three copies of chromosome 13, 18 or 21 instead of the normal two, and this improper balancing can cause trouble. For example, three copies of chromosome 21 lead to Down syndrome.

To make her work easier, Amonlike many other basic scientistsstudies yeast cells, which separate their chromosomes almost exactly the same way human cells do, except that yeast do it much faster. A yeast cell copies its DNA and produces daughter cells in about 1 1/2 hours, compared to a whole day for human cells.

The yeast cells she uses are the same kind bakeries use to make bread and breweries use to make beer!

Amon has made major progress in understanding the details of meiosis. Her research shows how, in healthy cells, gluelike protein complexes called cohesins release pairs of chromosomes at exactly the right time. This allows the chromosomes to separate properly.

These findings have important implications for understanding and treating infertility, birth defects and cancer.

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So, we've described DNAits basic properties and how our bodies make more of it. But how does DNA serve as the language of life? How do you get a protein from a gene?

There are two major steps in making a protein. The first is transcription, where the information coded in DNA is copied into RNA. The RNA nucleotides are complementary to those on the DNA: a C on the RNA strand matches a G on the DNA strand.

1. RNA polymerase transcribes DNA to make messenger RNA (mRNA). 2. The mRNA sequence (dark red strand) is complementary to the DNA sequence (blue strand). 3. On ribosomes, transfer RNA (tRNA) helps convert mRNA into protein. 4. Amino acids link up to make a protein.

The only difference is that RNA pairs a nucleotide called uracil (U), instead of a T, with an A on the DNA.

A protein machine called RNA polymerase reads the DNA and makes the RNA copy. This copy is called messenger RNA, or mRNA, because it delivers the gene's message to the protein-producing machinery.

At this point you may be wondering why all of the cells in the human body aren't exactly alike, since they all contain the same DNA.What makes a liver cell different from a brain cell? How do the cells in the heart make the organ contract, but those in skin allow us to sweat?

Cells can look and act differently, and do entirely different jobs, because each cell "turns on," or expresses, only the genes appropriate for what it needs to do.

RNA polymerase (green) and one end of a DNA strand (blue) are attached to clear beads pinned down in two optical traps. As RNA polymerase moves along the DNA, it creates an RNA copy of a gene, shown here as a pink strand. STEVEN BLOCK

That's because RNA polymerase does not work alone, but rather functions with the aid of many helper proteins. While the core part of RNA polymerase is the same in all cells, the helpers vary in different cell types throughout the body.

You'd think that for a process so essential to life, researchers would know a lot about how transcription works. While it's true that the basics are clearbiologists have been studying gene transcribing by RNA polymerases since these proteins were first discovered in 1960 some of the details are actually still murky.

The biggest obstacle to learning more has been a lack of tools. Until recently, researchers were unable to get a picture at the atomic level of the giant RNA polymerase protein assemblies inside cells to understand how the many pieces of this amazing, living machine do what they do, and do it so well.

But our understanding is improving fast, thanks to spectacular technological advances. We have new X-ray pictures that are far more sophisticated than those that revealed the structure of DNA. Roger Kornberg of Stanford University in California used such methods to determine the structure of RNA polymerase. This work earned him the 2006 Nobel Prize in chemistry. In addition, very powerful microscopes and other tools that allow us to watch one molecule at a time provide a new look at RNA polymerase while it's at work reading DNA and producing RNA.

For example, Steven Block, also of Stanford, has used a physics technique called optical trapping to track RNA polymerase as it inches along DNA. Block and his team performed this work by designing a specialized microscope sensitive enough to watch the real-time motion of a single polymerase traveling down a gene on one chromosome.

The researchers discovered that molecules of RNA polymerase behave like battery-powered spiders as they crawl along the DNA ladder, adding nucleotides one at a time to the growing RNA strand. The enzyme works much like a motor, Block believes, powered by energy released during the chemical synthesis of RNA.

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Genes are often interrupted by stretches of DNA (introns, blue) that do not contain instructions for making a protein. The DNA segments that do contain protein-making instructions are known as exons (green).

Several types of RNA play key roles in making a protein. The gene transcript (the mRNA) transfers information from DNA in the nucleus to the ribosomes that make protein. Ribosomal RNA forms about 60 percent of the ribosomes. Lastly, transfer RNA carries amino acids to the ribosomes. As you can see, all three types of cellular RNAs come together to produce new proteins.

But the journey from gene to protein isn't quite as simple as we've just made it out to be. After transcription, several things need to happen to mRNA before a protein can be made. For example, the genetic material of humans and other eukaryotes (organisms that have a nucleus) includes a lot of DNA that doesn't encode proteins. Some of this DNA is stuck right in the middle of genes.

To distinguish the two types of DNA, scientists call the coding sequences of genes exons and the pieces in between introns (for intervening sequences).

If RNA polymerase were to transcribe DNA from the start of an intron-containing gene to the end, the RNA would be complementary to the introns as well as the exons.

To get an mRNA molecule that yields a working protein, the cell needs to trim out the intron sections and then stitch only the exon pieces together (see drawing). This process is called RNA splicing.

Arranging exons in different patterns, called alternative splicing, enables cells to make different proteins from a single gene.

Splicing has to be extremely accurate. An error in the splicing process, even one that results in the deletion of just one nucleotide in an exon or the addition of just one nucleotide in an intron, will throw the whole sequence out of alignment. The result is usually an abnormal proteinor no protein at all. One form of Alzheimer's disease, for example, is caused by this kind of splicing error.

Molecular biologist Christine Guthrie of the University of California, San Francisco, wants to understand more fully the mechanism for removing intron RNA and find out how it stays so accurate.

She uses yeast cells for these experiments. Just like human DNA, yeast DNA has introns, but they are fewer and simpler in structure and are therefore easier to study. Guthrie can identify which genes are required for splicing by finding abnormal yeast cells that mangle splicing.

So why do introns exist, if they're just going to be chopped out? Without introns, cells wouldn't need to go through the splicing process and keep monitoring it to be sure it's working right.

As it turns out, splicing also makes it possible for cells to create more proteins.

Think about all the exons in a gene. If a cell stitches together exons 1, 2 and 4, leaving out exon 3, the mRNA will specify the production of a particular protein. But instead, if the cell stitches together exons 1, 2 and 3, this time leaving out exon 4, then the mRNA will be translated into a different protein (see drawing).

By cutting and pasting the exons in different patterns, which scientists call alternative splicing, a cell can create different proteins from a single gene. Alternative splicing is one of the reasons why human cells, which have about 20,000 genes, can make hundreds of thousands of different proteins.

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Until recently, researchers looked at genes, and the proteins they encode, one at a time. Now, they can look at how large numbers of genes and proteins act, as well as how they interact. This gives them a much better picture of what goes on in a living organism.

Already, scientists can identify all of the genes that are transcribed in a cellor in an organ, like the heart. And although researchers can't tell you, right now, what's going on in every cell of your body while you read a book or walk down the street, they can do this sort of "whole-body" scan for simpler, single-celled organisms like yeast.

Using a technique called genome-wide location analysis, Richard Young of the Massachusetts Institute of Technology unraveled a "regulatory code" of living yeast cells, which have more than 6,000 genes in their genome. Young's technique enabled him to determine the exact places where RNA polymerase's helper proteins sit on DNA and tell RNA polymerase to begin transcribing a gene.

Since he did the experiment with the yeast exposed to a variety of different conditions,Young was able to figure out how transcription patterns differ when the yeast cell is under stress (say, in a dry environment) or thriving in a sugary-rich nutrient solution. Done one gene at a time, using methods considered state-of-the-art just a few years ago, this kind of analysis would have taken hundreds of years.

After demonstrating that his technique worked in yeast, Young then took his research a step forward. He used a variation of the yeast method to scan the entire human genome in small samples of cells taken from the pancreases and livers of people with type 2 diabetes. He used the results to identify genes that aren't transcribed correctly in people with the disease.

This information provides researchers with an important tool for understanding how diabetes and other diseases are influenced by defective genes. By building models to predict how genes respond in diverse situations, researchers may be able to learn how to stop or jump-start genes on demand, change the course of a disease or prevent it from ever happening.

While most genetic research uses lab organisms, test tubes and petri dishes, the results have real consequences for people. Your first encounter with genetic analysis probably happened shortly after you were born, when a doctor or nurse took a drop of blood from the heel of your tiny foot.

Lab tests performed with that single drop of blood can diagnose certain rare genetic disorders as well as metabolic problems like phenylketonuria (PKU).

Screening newborns in this way began in the 1960s in Massachusetts with testing for PKU, a disease affecting 1 in 14,000 people. PKU is caused by an enzyme that doesn't work properly due to a genetic mutation. Those born with this disorder cannot metabolize the amino acid phenylalanine, which is present in many foods. Left untreated, PKU can lead to mental retardation and neurological damage, but a special diet can prevent these outcomes. Testing for this condition has made a huge difference in many lives.

Newborn screening is governed by individual states. This means that the state in which a baby is born determines the genetic conditions for which he or she will be screened. Currently, states test for between 28 and 54 conditions. All states test for PKU.

Although expanded screening for genetic diseases in newborns is advocated by some, others question the value of screening for conditions that are currently untreatable. Another issue is that some children with mild versions of certain genetic diseases may be treated needlessly.

In 2006, the Advisory Committee on Heritable Disorders in Newborns and Children, which assists the Secretary of the U.S. Department of Health and Human Services, recommended a standard, national set of newborn tests for 29 conditions, ranging from relatively common hearing problems to very rare metabolic diseases.

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A ribosome consists of large and small protein subunits with transfer RNAs nestled in the middle. RIBOSOME STRUCTURE COURTESY OF JAMIE CATE, MARAT YUSUPOV, GULNARA YUSUPOVA, THOMAS EARNEST AND HARRY NOLLER. GRAPHIC COURTESY OF ALBION BAUCOM, UNIVERSITY OF CALIFORNIA, SANTA CRUZ.

After a gene has been read by RNA polymerase and the RNA is spliced, what happens next in the journey from gene to protein? The next step is reading the RNA information and fitting the building blocks of a protein together. This is called translation, and its principal actors are the ribosome and amino acids.

Ribosomes are among the biggest and most intricate structures in the cell. The ribosomes of bacteria contain not only huge amounts of RNA, but also more than 50 different proteins. Human ribosomes have even more RNA and between 70 and 80 different proteins!

Harry Noller of the University of California, Santa Cruz, has found that a ribosome performs several key jobs when it translates the genetic code of mRNA. As the messenger RNA threads through the ribosome protein machine, the ribosome reads the mRNA sequence and helps recognize and recruit the correct amino acid-carrying transfer RNA to match the mRNA code. The ribosome also links each additional amino acid into a growing protein chain (see drawing).

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