Base-pairing rules are the observed pairings of bases whenstrands of DNA, RNA, or both, pair with each other. Bases followthese rules during DNA replication, transcription, translation(pairing between messenger RNA and transfer RNA), and when primersand probes are active.

• What Are The Nitrogenous Base Pairing Rules For Dna
• What Are The Dna Base Pairing Rules Definition
• Rna Base Pairs

Cytosine and guanine, when base paired, have three hydrogen bonds between them. Adenine and thymine only have two. This extra hydrogen bond helps make the cytosine-guanine pair favorable because it increases stability, and reduces bond energy. Ionic and covalent bonds do not occur between nitrogenous bases in DNA. In any DNA sample, there are four bases that pair in only one way: adenine and thymine, guanine and cytosine. They total 100 percent of the sample. Chargaff's rule states that the concentration for each base in a base pair is always equal to its mate, so the concentration of adenine equals the concentration of thymine, for example.

The base pairing rules for DNA are * A pairs with T * Gpairs with C * C pairs with G * T pairs with A The base pairingrules for DNA (left) with RNA (right) are: * A pairswith U * G pairs with C * C pairs with G * T pairs with A When twomolecules of RNA pair, the rules are: * A pairs with U * Gpairs with C * C pairs with G * U pairs with A

How are base pairing rules and complementary base rules related?

Base pairing rules and complementary base rules are related because of DNA. If one can find the base pairing on a strand of DNA, usually the complementary base is easily found.

What are the correct base-pairing rules of DNA?

The correct base-pairing rules ofr DNA. . . The base pairing rules for DNA are A pairs with T G pairs with C C pairs with G T pairs with A

Relate the base pairing rules to the structure of DNA?

The relationship of base pairing rules to the structure of DNA was observed by Rosalind Franklin. This observation was of purine pairing with pyrimidine that gives constant width to DNA structure.

What scientist are credited with the base pairing rules?

James Watson and Francis Crick are credited with the base pairing rules and DNA structure in general. Erwin Chargaff is credited with the rules of base pairs in that the number of pyrimidines is equal to the number of purines.

What scientists are credited with the base pairing rules?

James Watson and Francis Crick are credited with the base pairing rules and DNA structure in general. Erwin Chargaff is credited with the rules of base pairs in that the number of pyrimidines is equal to the number of purines.

How are DNA bases always paired?

The base pairing rule is known as complementary base pairing. In DNA, the following base pairing rules apply: Adenine (A) pairs with Thymine (T) Cytosine (C) pairs with Guanine (G) In RNA, Uracil replaced Thymine so the base pairing rules here become Uracal (U) to Adenine (A).

Which samples support the base pairing rules?

A and t have to be the same and g and c have to be the same

What are the base pairing rules for DNA?

Adenine pairs with thymine Guanine pairs with cytosine

What are the base pairing rules?

- A with T: Adenine & Thymine C with G: Cytosine & Guanine

Base pairing rules for DNA?

cytosine pairs with guanine. adenine pairs with thymine

Why are the base pairing rules different between replication and transcription?

Replication involves DNA pairing with DNA, but transcription involves DNA pairing with RNA. Replication means copying, and it applies to DNA. The two strands in a molecule of DNA separate, and a new strand of DNA is built (synthesized) along each, using the base pairing rules: A (adenine) with T (thymine); C (cytosine) with G (guanine). Transcription means the synthesis of a molecule of RNA along one of the strands of DNA. The base pairing… Read More

What are the correct base pairing rules of the DNA?

Adenine pairs with thymine, and cytosine pairs with guanine.

What pairs with what during DNA replication?

DNA polymerases add nucleotides to the exposed base pairs according to base-pairing rules.

What is the base-pairing rules to the structure of DNA?

Adenine pairs with thymine Guanine pairs with cytosine.

What are the DNA base pairing rules?

Adenine always pairs with thymine Cytosine always pairs with guanine.

What are the correct base-pairing rules for DNA?

adenine bonds to thymine and guanine bonds to cytosine

What bases pair according to the rules of base pairing?

adenine bonds to thymine cytosine bonds to guanine.

Transcription follows the same base-pairing rules as DNA replication except for cytosine which has a different partner?

This is false transcription does not follows the same base-pairing rules as DNA replication except for cytosine which has a different partner. Transcription begins with an enzyme called RNA polymerase.

What are the base-pairing rules for DNA?

The base pairing-rules for DNA are that, only the Nitrogen Bases of DNA which are; Adenine 'A'-which only pairs with-Thymine 'T', and Cytosine 'C'-which only pairs with-Guanine 'G' can only pair to one another within that sequence. Posted By; JoelBaum24

How is an accurate new copy of DNA formed?

DNA polymerases add nucleotides to the exposed base pairs according to base-pairing rules

How do the base pairing rules relate to chargaff's rules?

Chargaff's rule means that there should be the same number of purine and pyrimidine bases in DNA. The base pairing rules means that A always pairs with T, and G always pairs with C ie. a purine always pairs with a pyrimidine, so there must be the same number of both proving Chargaff's rule.

Which two scientists figured out the base-pairing rules?

Ernest Chargaff (Austrian) and Waclaw Szybalski (Polish).

What is translation when speaking of protein synthesis?

tRNA is changed into amino acids following nitrogen base pairing rules.

Which anticodon pairs with gau?

The answer is AUC. Anti codons follow regular base-pairing rules, but they are also mirrored horizontally. Standard base pairing would dictate the answer be CUA, but anti codon is instead AUC. The previous answer was misleading and incorrect.

Complementary base pairing links what?

Nucleotides and linked by complementary base pairing.

During DNA replication how is an accurate copy of DNA formed?

DNA polymerases add nucleotides to the exposed base pairs according to base-pairing rules.

Who discovered the base pairing rules in DNA?

Erwin Chargaff, who created 'Chargaff's Ratios' to show that A=T and C=G.

What are the base pairing rules for the transcription of Dna?

Adenine pairs with Thymine, and Cytosine pairs with Guanine. An example: AATTGCGATCAAT TTAACGCTAGTTA.

What is the bonding of base pairing rules?

Purines always bond with Pyrimidines. Adenine bonds with Thymine. Guanine bonds with Cytosine.

Why is complementary base pairing crucial for life?

Why is complementary base pairing crucial for life?

What are the correct base pairing rules for DNA?

A purine (adenosine & guanine) will base pair with a pyrimidine (thymine and cytosine). Adenosine will always pair with thymine and guanosine with cytosine.

What is meant by the term base pairing?

Base pairing is when DNA is double helix and genes are paired.

Explain the role of complementary base pairing in the precise replication process of DNA

In this outcome, we’ll learn more about the precise structure of DNA and how it replicates.

Learning Objectives

• Understand the historical basis of our understanding of DNA
• Outline the basic steps in DNA replication
• Identify the major enzymes that play a role in DNA replication
• Identify the key proofreading processes in DNA replication
• Understand the basic role of telomeres in protecting DNA from replication errors

The History of DNA

Figure 1. Friedrich Miescher (1844–1895) discovered nucleic acids.

Modern understandings of DNA have evolved from the discovery of nucleic acid to the development of the double-helix model. In the 1860s, Friedrich Miescher (Figure 1), a physician by profession, was the first person to isolate phosphate-rich chemicals from white blood cells or leukocytes. He named these chemicals (which would eventually be known as RNA and DNA) nuclein because they were isolated from the nuclei of the cells.

To see Miescher conduct an experiment step-by-step, click through this review of how he discovered the key role of DNA and proteins in the nucleus.

A half century later, British bacteriologist Frederick Griffith was perhaps the first person to show that hereditary information could be transferred from one cell to another “horizontally,” rather than by descent. In 1928, he reported the first demonstration of bacterial transformation, a process in which external DNA is taken up by a cell, thereby changing morphology and physiology. He was working with Streptococcus pneumoniae, the bacterium that causes pneumonia. Griffith worked with two strains, rough (R) and smooth (S). The R strain is non-pathogenic (does not cause disease) and is called rough because its outer surface is a cell wall and lacks a capsule; as a result, the cell surface appears uneven under the microscope. The S strain is pathogenic (disease-causing) and has a capsule outside its cell wall. As a result, it has a smooth appearance under the microscope. Griffith injected the live R strain into mice and they survived. In another experiment, when he injected mice with the heat-killed S strain, they also survived. In a third set of experiments, a mixture of live R strain and heat-killed S strain were injected into mice, and—to his surprise—the mice died. Upon isolating the live bacteria from the dead mouse, only the S strain of bacteria was recovered. When this isolated S strain was injected into fresh mice, the mice died. Griffith concluded that something had passed from the heat-killed S strain into the live R strain and transformed it into the pathogenic S strain, and he called this the transforming principle (Figure 2). These experiments are now famously known as Griffith’s transformation experiments.

Figure 2. Two strains of S. pneumoniae were used in Griffith’s transformation experiments. The R strain is non-pathogenic. The S strain is pathogenic and causes death. When Griffith injected a mouse with the heat-killed S strain and a live R strain, the mouse died. The S strain was recovered from the dead mouse. Thus, Griffith concluded that something had passed from the heat-killed S strain to the R strain, transforming the R strain into S strain in the process. (credit “living mouse”: modification of work by NIH; credit “dead mouse”: modification of work by Sarah Marriage)

What Are The Nitrogenous Base Pairing Rules For Dna

Scientists Oswald Avery, Colin MacLeod, and Maclyn McCarty (1944) were interested in exploring this transforming principle further. They isolated the S strain from the dead mice and isolated the proteins and nucleic acids, namely RNA and DNA, as these were possible candidates for the molecule of heredity. They conducted a systematic elimination study. They used enzymes that specifically degraded each component and then used each mixture separately to transform the R strain. They found that when DNA was degraded, the resulting mixture was no longer able to transform the bacteria, whereas all of the other combinations were able to transform the bacteria. This led them to conclude that DNA was the transforming principle.

Forensic Scientists and DNA Analysis

DNA evidence was used for the first time to solve an immigration case. The story started with a teenage boy returning to London from Ghana to be with his mother. Immigration authorities at the airport were suspicious of him, thinking that he was traveling on a forged passport. After much persuasion, he was allowed to go live with his mother, but the immigration authorities did not drop the case against him. All types of evidence, including photographs, were provided to the authorities, but deportation proceedings were started nevertheless. Around the same time, Dr. Alec Jeffreys of Leicester University in the United Kingdom had invented a technique known as DNA fingerprinting. The immigration authorities approached Dr. Jeffreys for help. He took DNA samples from the mother and three of her children, plus an unrelated mother, and compared the samples with the boy’s DNA. Because the biological father was not in the picture, DNA from the three children was compared with the boy’s DNA. He found a match in the boy’s DNA for both the mother and his three siblings. He concluded that the boy was indeed the mother’s son.

Forensic scientists analyze many items, including documents, handwriting, firearms, and biological samples. They analyze the DNA content of hair, semen, saliva, and blood, and compare it with a database of DNA profiles of known criminals. Analysis includes DNA isolation, sequencing, and sequence analysis; most forensic DNA analysis involves polymerase chain reaction (PCR) amplification of short tandem repeat (STR) loci and electrophoresis to determine the length of the PCR-amplified fragment. Only mitochondrial DNA is sequenced for forensics. Forensic scientists are expected to appear at court hearings to present their findings. They are usually employed in crime labs of city and state government agencies. Geneticists experimenting with DNA techniques also work for scientific and research organizations, pharmaceutical industries, and college and university labs. Students wishing to pursue a career as a forensic scientist should have at least a bachelor’s degree in chemistry, biology, or physics, and preferably some experience working in a laboratory.

Experiments conducted by Martha Chase and Alfred Hershey in 1952 provided confirmatory evidence that DNA was the genetic material and not proteins. Chase and Hershey were studying a bacteriophage, which is a virus that infects bacteria. Viruses typically have a simple structure: a protein coat, called the capsid, and a nucleic acid core that contains the genetic material, either DNA or RNA. The bacteriophage infects the host bacterial cell by attaching to its surface, and then it injects its nucleic acids inside the cell. The phage DNA makes multiple copies of itself using the host machinery, and eventually the host cell bursts, releasing a large number of bacteriophages. Hershey and Chase labeled one batch of phage with radioactive sulfur, ³⁵S, to label the protein coat. Another batch of phage were labeled with radioactive phosphorus, ³²P. Because phosphorous is found in DNA, but not protein, the DNA and not the protein would be tagged with radioactive phosphorus.

Each batch of phage was allowed to infect the cells separately. After infection, the phage bacterial suspension was put in a blender, which caused the phage coat to be detached from the host cell. The phage and bacterial suspension was spun down in a centrifuge. The heavier bacterial cells settled down and formed a pellet, whereas the lighter phage particles stayed in the supernatant. In the tube that contained phage labeled with ³⁵S, the supernatant contained the radioactively labeled phage, whereas no radioactivity was detected in the pellet. In the tube that contained the phage labeled with ³²P, the radioactivity was detected in the pellet that contained the heavier bacterial cells, and no radioactivity was detected in the supernatant. Hershey and Chase concluded that it was the phage DNA that was injected into the cell and carried information to produce more phage particles, thus providing evidence that DNA was the genetic material and not proteins (Figure 3).

Figure 3. In Hershey and Chase’s experiments, bacteria were infected with phage radiolabeled with either ³⁵S, which labels protein, or ³²P, which labels DNA. Only ³²P entered the bacterial cells, indicating that DNA is the genetic material.

Around this same time, Austrian biochemist Erwin Chargaff examined the content of DNA in different species and found that the amounts of adenine, thymine, guanine, and cytosine were not found in equal quantities, and that it varied from species to species, but not between individuals of the same species. He found that the amount of adenine equals the amount of thymine, and the amount of cytosine equals the amount of guanine, or A = T and G = C. This is also known as Chargaff’s rules. This finding proved immensely useful when Watson and Crick were getting ready to propose their DNA double helix model.

Practice Question

The experiments by Hershey and Chase helped confirm that DNA was the hereditary material on the basis of the finding that:

1. radioactive phage were found in the pellet
2. radioactive cells were found in the supernatant
3. radioactive sulfur was found inside the cell
4. radioactive phosphorus was found in the cell

Basics of DNA Replication

Figure 4. The three suggested models of DNA replication. Grey indicates the original DNA strands, and blue indicates newly synthesized DNA.

The elucidation of the structure of the double helix provided a hint as to how DNA divides and makes copies of itself. This model suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied. What was not clear was how the replication took place. There were three models suggested: conservative, semi-conservative, and dispersive (see Figure 4).

In conservative replication, the parental DNA remains together, and the newly formed daughter strands are together. The semi-conservative method suggests that each of the two parental DNA strands act as a template for new DNA to be synthesized; after replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. In the dispersive model, both copies of DNA have double-stranded segments of parental DNA and newly synthesized DNA interspersed.

Meselson and Stahl were interested in understanding how DNA replicates. They grew E. coli for several generations in a medium containing a “heavy” isotope of nitrogen (¹⁵N) that gets incorporated into nitrogenous bases, and eventually into the DNA (Figure 5).

Figure 5. Meselson and Stahl experimented with E. coli grown first in heavy nitrogen (¹⁵N) then in ¹⁴N. DNA grown in ¹⁵N (red band) is heavier than DNA grown in ¹⁴N (orange band), and sediments to a lower level in cesium chloride solution in an ultracentrifuge. When DNA grown in ¹⁵N is switched to media containing ¹⁴N, after one round of cell division the DNA sediments halfway between the ¹⁵N and ¹⁴N levels, indicating that it now contains fifty percent ¹⁴N. In subsequent cell divisions, an increasing amount of DNA contains ¹⁴N only. This data supports the semi-conservative replication model. (credit: modification of work by Mariana Ruiz Villareal)

The E. coli culture was then shifted into medium containing ¹⁴N and allowed to grow for one generation. The cells were harvested and the DNA was isolated. The DNA was centrifuged at high speeds in an ultracentrifuge. Some cells were allowed to grow for one more life cycle in ¹⁴N and spun again. During the density gradient centrifugation, the DNA is loaded into a gradient (typically a salt such as cesium chloride or sucrose) and spun at high speeds of 50,000 to 60,000 rpm. Under these circumstances, the DNA will form a band according to its density in the gradient. DNA grown in ¹⁵N will band at a higher density position than that grown in ¹⁴N. Meselson and Stahl noted that after one generation of growth in ¹⁴N after they had been shifted from ¹⁵N, the single band observed was intermediate in position in between DNA of cells grown exclusively in ¹⁵N and ¹⁴N. This suggested either a semi-conservative or dispersive mode of replication. The DNA harvested from cells grown for two generations in ¹⁴N formed two bands: one DNA band was at the intermediate position between ¹⁵N and ¹⁴N, and the other corresponded to the band of ¹⁴N DNA. These results could only be explained if DNA replicates in a semi-conservative manner. Therefore, the other two modes were ruled out.

During DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are copied. The new strand will be complementary to the parental or “old” strand. When two daughter DNA copies are formed, they have the same sequence and are divided equally into the two daughter cells.

Major Enzymes

The process of DNA replication is catalyzed by a type of enzyme called DNA polymerase (poly meaning many, mer meaning pieces, and –ase meaning enzyme; so an enzyme that attaches many pieces of DNA). Observe Figure 6: the double helix of the original DNA molecule separates (blue) and new strands are made to match the separated strands. The result will be two DNA molecules, each containing an old and a new strand. Therefore, DNA replication is called semiconservative. The term semiconservative refers to the fact that half of the original molecule (one of the two strands in the double helix) is “conserved” in the new molecule. The original strand is referred to as the template strand because it provides the information, or template, for the newly synthesized strand.

Figure 6. By Madprime(wikipedia) (DNA replication split horizontal) CC BY-SA 2.0

DNA replication relies on the double-stranded nature of the molecule. One double stranded DNA molecule, when replicated, will become two double-stranded molecules, each containing one original strand and one newly synthesized strand. You remember that the two strands of DNA run antiparallel: one from the 5′ to the 3′, and the other from the 3′ to the 5′. The synthesis of the new DNA strand can only happen in one direction: from the 5′ to the 3′ end. In other words, the new bases are always added to the 3′ end of the newly synthesized DNA strand. So if the new nucleotide is always added to the 3′ end of an existing nucleotide, where does the first nucleotide come from? In fact, DNA polymerase needs an “anchor” to start adding nucleotides: a short sequence of DNA or RNA that is complementary to the template strand will work to provide a free 3′ end. This sequence is called a primer (Figure 7).

How does DNA polymerase know in what order to add nucleotides? Specific base pairing in DNA is the key to copying the DNA: if you know the sequence of one strand, you can use base pairing rules to build the other strand. Bases form pairs (base pairs) in a very specific way. Figure 8 shows how A (adenine) pairs with T (thymine) and G (guanine) pairs with C (cytosine). It is important to remember that this binding is specific: T pairs with A, but not with C. The molecular recognition occurs because of the ability of bases to form specific hydrogen bonds: atoms align just right to make hydrogen bonds possible. Also note that a larger base (purine, A or G) always pairs with a smaller base (pyrimidine, C or T).

Figure 8. DNA chemical structure. Modification of DNA chemical structure by Madeleine Price Ball; CC-BY-SA-2.0

Practice Questions

True/False: DNA replication requires an enzyme.

What are the building blocks on DNA? Sims 3 hybrid.

What Are The Dna Base Pairing Rules Definition

1. Deoxyribonucleotides
2. Fatty acids
3. Ribonucleotides
4. Amino acids

True/False: DNA replication requires energy.

We have the building blocks, a source of energy, and a catalyst. What’s missing? We need instruction about the order of nucleotides in the new polymer. Which molecule provides these instructions?

1. Protein
2. DNA
3. Carbohydrate
4. Lipid

There is one more thing required by the DNA polymerase. It cannot just start making a DNA copy of the template strand; it needs a short piece of DNA or RNA with a free hydroxyl group in the right place to attach the nucleotides to. (Remember that synthesis always occurs in one direction—new building blocks are added to the 3′ end.) This component starts the process by giving DNA polymerase something to bind to. What might you call this short piece of nucleic acid?

1. A solvent
2. A primer
3. A converter
4. A sealant

Now that you understand the basics of DNA replication, we can add a bit of complexity. The two strands of DNA have to be temporarily separated from each other; this job is done by a special enzyme, helicase, that helps unwind and separate the DNA helices (Figure 9). Another issue is that the DNA polymerase only works in one direction along the strand (5′ to 3′), but the double-stranded DNA has two strands oriented in opposite directions. This problem is solved by synthesizing the two strands slightly differently: one new strand grows continuously, the other in bits and pieces. Short fragments of RNA are used as primers for the DNA polymerase.

Figure 9. By Mariana Ruiz (DNA replication) Public Domain

Practice Questions

Which of these separates the two complementary strands of DNA?

1. DNA polymerase
2. helicase
3. RNA primer
4. single-strand binding protein

Which of these attaches complementary bases to the template strand?

1. DNA polymerase
2. helicase
3. RNA primer
4. single-strand binding protein

Which of these is later replaced with DNA bases?

Rna Base Pairs

1. DNA polymerase
2. helicase
3. RNA primer
4. single-strand binding protein

Table 1 summarizes the roles of different enzymes in DNA replication:

“Proofreading” DNA

DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.

Most of the mistakes during DNA replication are promptly corrected by DNA polymerase by proofreading the base that has been just added (Figure 10). In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the exonuclease action of DNA pol III. Once the incorrect nucleotide has been removed, a new one will be added again.

Figure 10. Proofreading by DNA polymerase corrects errors during replication.

Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair (Figure 11). The enzymes recognize the incorrectly added nucleotide and excise it; this is then replaced by the correct base. If this remains uncorrected, it may lead to more permanent damage. How do mismatch repair enzymes recognize which of the two bases is the incorrect one? In E. coli, after replication, the nitrogenous base adenine acquires a methyl group; the parental DNA strand will have methyl groups, whereas the newly synthesized strand lacks them. Thus, DNA polymerase is able to remove the wrongly incorporated bases from the newly synthesized, non-methylated strand. In eukaryotes, the mechanism is not very well understood, but it is believed to involve recognition of unsealed nicks in the new strand, as well as a short-term continuing association of some of the replication proteins with the new daughter strand after replication has completed.

Figure 11. In mismatch repair, the incorrectly added base is detected after replication. The mismatch repair proteins detect this base and remove it from the newly synthesized strand by nuclease action. The gap is now filled with the correctly paired base.

In another type of repair mechanism, nucleotide excision repair, enzymes replace incorrect bases by making a cut on both the 3′ and 5′ ends of the incorrect base (Figure 12).

Figure 12. Nucleotide excision repairs thymine dimers. When exposed to UV, thymines lying adjacent to each other can form thymine dimers. In normal cells, they are excised and replaced.

The segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase. This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers.

Telomeres

As you’ve learned, the enzyme DNA pol can add nucleotides only in the 5′ to 3′ direction. In the leading strand, synthesis continues until the end of the chromosome is reached. On the lagging strand, DNA is synthesized in short stretches, each of which is initiated by a separate primer. When the replication fork reaches the end of the linear chromosome, there is no place for a primer to be made for the DNA fragment to be copied at the end of the chromosome. These ends thus remain unpaired, and over time these ends may get progressively shorter as cells continue to divide.

The ends of the linear chromosomes are known as telomeres, which have repetitive sequences that code for no particular gene. In a way, these telomeres protect the genes from getting deleted as cells continue to divide. In humans, a six base pair sequence, TTAGGG, is repeated 100 to 1000 times. The discovery of the enzyme telomerase (Figure 13) helped in the understanding of how chromosome ends are maintained. The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and complementary bases to the RNA template are added on the 3′ end of the DNA strand. Once the 3′ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. Thus, the ends of the chromosomes are replicated.

Figure 13. The ends of linear chromosomes are maintained by the action of the telomerase enzyme.

Figure 14. Elizabeth Blackburn, 2009 Nobel Laureate, is the scientist who discovered how telomerase works. (credit: US Embassy Sweden)

Telomerase is typically active in germ cells and adult stem cells. It is not active in adult somatic cells. For her discovery of telomerase and its action, Elizabeth Blackburn (Figure 14) received the Nobel Prize for Medicine and Physiology in 2009.

Telomerase and Aging

Cells that undergo cell division continue to have their telomeres shortened because most somatic cells do not make telomerase. This essentially means that telomere shortening is associated with aging. With the advent of modern medicine, preventative health care, and healthier lifestyles, the human life span has increased, and there is an increasing demand for people to look younger and have a better quality of life as they grow older.

In 2010, scientists found that telomerase can reverse some age-related conditions in mice. This may have potential in regenerative medicine.^[1] Telomerase-deficient mice were used in these studies; these mice have tissue atrophy, stem cell depletion, organ system failure, and impaired tissue injury responses. Telomerase reactivation in these mice caused extension of telomeres, reduced DNA damage, reversed neurodegeneration, and improved the function of the testes, spleen, and intestines. Thus, telomere reactivation may have potential for treating age-related diseases in humans.

Cancer is characterized by uncontrolled cell division of abnormal cells. The cells accumulate mutations, proliferate uncontrollably, and can migrate to different parts of the body through a process called metastasis. Scientists have observed that cancerous cells have considerably shortened telomeres and that telomerase is active in these cells. Interestingly, only after the telomeres were shortened in the cancer cells did the telomerase become active. If the action of telomerase in these cells can be inhibited by drugs during cancer therapy, then the cancerous cells could potentially be stopped from further division.

In Summary: DNA Base Pairs and Replication

DNA was first isolated from white blood cells by Friedrich Miescher, who called it nuclein because it was isolated from nuclei. Frederick Griffith’s experiments with strains of Streptococcus pneumoniae provided the first hint that DNA may be the transforming principle. Avery, MacLeod, and McCarty proved that DNA is required for the transformation of bacteria. Later experiments by Hershey and Chase using bacteriophage T2 proved that DNA is the genetic material. Chargaff found that the ratio of A = T and C = G, and that the percentage content of A, T, G, and C is different for different species.

The model for DNA replication suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied. In conservative replication, the parental DNA is conserved, and the daughter DNA is newly synthesized. The semi-conservative method suggests that each of the two parental DNA strands acts as template for new DNA to be synthesized; after replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. The dispersive mode suggested that the two copies of the DNA would have segments of parental DNA and newly synthesized DNA. Experimental evidence showed DNA replication is semi-conservative.

Replication in eukaryotes starts at multiple origins of replication. A primer is required to initiate synthesis, which is then extended by DNA polymerase as it adds nucleotides one by one to the growing chain. The leading strand is synthesized continuously, whereas the lagging strand is synthesized in short stretches called Okazaki fragments. The RNA primers are replaced with DNA nucleotides; the DNA remains one continuous strand by linking the DNA fragments with DNA ligase. Below is a summary table of the major enzymes addressed in this reading, listed in rough order of activity during replication.

The ends of the chromosomes pose a problem during DNA replication as polymerase is unable to extend them without a primer. Telomerase, an enzyme with a built-in RNA template, extends the ends by copying the RNA template and extending one end of the chromosome. DNA polymerase can then extend the DNA using the primer. In this way, the ends of the chromosomes are protected. This is important as evidence indicates telomere length may play a role in regulating cell division and the process of aging.

Check Your Understanding

Answer the question(s) below to see how well you understand the topics covered in the previous section. This short quiz does not count toward your grade in the class, and you can retake it an unlimited number of times.

Use this quiz to check your understanding and decide whether to (1) study the previous section further or (2) move on to the next section.

1. Jaskelioff et al., “Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice,” Nature 469 (2011): 102–7. ↵