DNA Replication

The law of complementary base pairing shows that we can predict the base sequence of one DNA strand if we know the sequence of the other. More importantly, it enables a

Saladin: Anatomy & Physiology: The Unity of Form and Function, Third Edition

4. Genetics and Cellular Function

Text

© The McGraw-H Companies, 2003

140 Part One Organization of the Body

140 Part One Organization of the Body

Cisterna

Ribosomes

Protein synthesis (translation)

Rough endoplasmic reticulum

Cisterna

Transport vesicle

Transport vesicle

Clathrin coat Protein folding

Golgi

Clathrin coat Protein folding

Removal of leader sequence

Ribosomes

Protein synthesis (translation)

Rough endoplasmic reticulum

Golgi

Removal of leader sequence

Secreted protein

Figure 4.10 Protein Packaging and Secretion. Some proteins are synthesized by ribosomes on the rough ER and carried in transport vesicles to the nearest cisterna of the Golgi complex. The Golgi complex modifies the structure of the protein, transferring it from one cisterna to the next, and finally packages it in Golgi vesicles. Some Golgi vesicles may remain within the cell and become lysosomes, while others may migrate to the plasma membrane and release the cell product by exocytosis.

Secreted protein

Figure 4.10 Protein Packaging and Secretion. Some proteins are synthesized by ribosomes on the rough ER and carried in transport vesicles to the nearest cisterna of the Golgi complex. The Golgi complex modifies the structure of the protein, transferring it from one cisterna to the next, and finally packages it in Golgi vesicles. Some Golgi vesicles may remain within the cell and become lysosomes, while others may migrate to the plasma membrane and release the cell product by exocytosis.

Table 4.3 Some Destinations and

Functions of Newly

Synthesized Proteins

Destination or Function

Proteins (examples)

Deposited as a structural protein

Actin of cytoskeleton

within cells

Keratin of epidermis

Used in the cytosol as a metabolic

ATPase

enzyme

Kinases

Returned to the nucleus for use in

Histones of chromatin

nuclear metabolism

RNA polymerase

Packaged in lysosomes for

Numerous lysosomal enzymes

autophagy, intracellular digestion,

and other functions

Delivered to other organelles for

Catalase of peroxisomes

intracellular use

Mitochondrial enzymes

Delivered to plasma membrane to

Hormone receptors

serve transport and other

Sodium-potassium pumps

functions

Secreted by exocytosis for

Digestive enzymes

extracellular functions

Casein of breast milk

cell to reproduce one strand based on information in the other. This immediately occurred to Watson and Crick when they discovered the structure of DNA. Watson was hesitant to make such a grandiose claim in their first publication, but Crick implored, "Well, we've got to say something! Otherwise people will think these two unknown chaps are so dumb they don't even realize the implications of their own work!" Thus, the last sentence of their first paper modestly stated, "It has not escaped our notice that the specific pairing we have postulated . . . immediately suggests a possible copying mechanism for the genetic material." Five weeks later they published a second paper pressing this point more vigorously.

The basic idea of DNA replication is evident from its base pairing, but the way in which DNA is organized in the chromatin introduces some complications that were not apparent when Watson and Crick first wrote. The fundamental steps of the replication process are as follows:

  1. The double helix unwinds from the histones.
  2. Like a zipper, an enzyme called DNA helicase opens up a short segment of the helix, exposing its nitrogenous bases. The point where one strand of DNA is "unzipped" and separates from its

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Physiology: The Unity of Function Companies, 2003 Form and Function, Third Edition

Chapter 4 Genetics and Cellular Function 141

Chapter 4 Genetics and Cellular Function 141

New DNA
Double Helix Watson Norton Third Edition

Figure 4.11 Semiconservative DNA Replication. (a) At the replication fork, DNA helicase (not shown) unwinds the double helix and exposes the bases. DNA polymerases begin assembling new bases across from the existing ones, moving away from the replication fork on one strand and toward it on the other strand. (b) The result is two DNA double helices, each composed of one strand of the original DNA and one newly synthesized strand.

Figure 4.11 Semiconservative DNA Replication. (a) At the replication fork, DNA helicase (not shown) unwinds the double helix and exposes the bases. DNA polymerases begin assembling new bases across from the existing ones, moving away from the replication fork on one strand and toward it on the other strand. (b) The result is two DNA double helices, each composed of one strand of the original DNA and one newly synthesized strand.

complementary strand is called a replication fork (fig. 4.11a).

An enzyme called DNA polymerase moves along the opened strands, reads the exposed bases, and like a matchmaker, arranges "marriages" with complementary free nucleotides in the nucleoplasm. If the polymerase finds the sequence TCG, for example, it assembles AGC across from it. One polymerase molecule moves away from the replication fork replicating one strand of the opened DNA, and another polymerase molecule moves in the opposite direction, replicating the other strand. Thus, from the old DNA molecule, two new ones are made. Each new DNA consists of one new helix synthesized from free nucleotides and one helix conserved from the parent DNA (fig. 4.11b). The process is therefore called semiconservative replication.

4. While DNA is synthesized in the nucleus, new histones are synthesized in the cytoplasm. Millions of histones are transported into the nucleus within a few minutes after DNA replication, and each new DNA helix wraps around them to make new nucleosomes.

Despite the complexity of this process, each DNA polymerase works at an impressive rate of about 100 base pairs per second. Even at this rate, however, it would take weeks for one polymerase molecule to replicate even one chromosome. But in reality, thousands of polymerase molecules work simultaneously on each DNA molecule and all 46 chromosomes are replicated in a mere 6 to 8 hours.

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