Chapter 16- Lecture Outline Flashcards
In 1953, James Watson and Francis Crick introduced an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA
Hereditary information is encoded in DNA and reproduced in all cells of the body
This DNA program directs the development of biochemical, anatomical, physiological, and
(to some extent) behavioral traits
DNA is copied____________________during and cells can repair their DNA
DNA replication,
Early in the 20th century, the identification of the molecules of inheritance loomed as a major challenge to biologists
DNA is the genetic material
When T. H. Morgan’s group showed that genes are located on chromosomes, the two components of chromosomes—DNA and protein—became candidates for the genetic material
The role of DNA in heredity was first discovered
by studying bacteria and the viruses that
infect them
The discovery of the genetic role of DNA began with research by Frederick Griffith in 1928
Griffith worked with two strains of a bacterium, one pathogenic and one harmless
When he mixed heat-killed remains of the pathogenic strain with living cells of the harmless strain, some living cells became pathogenic
He called this phenomenon transformation, now defined as a change in genotype and phenotype due to assimilation of foreign DNA
In 1944, Oswald Avery, Maclyn McCarty, and Colin MacLeod announced that the transforming substance was DNA
Many biologists remained skeptical, mainly because little was known about DNA
More evidence for DNA as the genetic material came from studies of viruses that infect bacteria
Such viruses, called bacteriophages (or phages), are widely used in molecular genetics research
A virus is DNA (sometimes RNA) enclosed by a protective coat, often simply protein
In 1952, Alfred Hershey and Martha Chase showed that DNA is the genetic material of a phage known as T2
They designed an experiment showing that only one of the two components of T2 (DNA or protein) enters an E. coli cell during infection
They concluded that the injected DNA of the phage provides
the genetic information
Two findings became known as Chargaff’s rules
The base composition of DNA varies between species
In any species the number of A and T bases are equal and the number of G and C bases are equal
rules was not understood until the discovery of
the double helix
After DNA was accepted as the genetic material, the challenge was to determine how its structure accounts for its role in heredity
Maurice Wilkins and Rosalind Franklin were using a technique called X-ray crystallography to study molecular structure
Franklin produced a picture of the DNA molecule using this technique
Watson and Crick built models of a double helix to conform to the X-rays and chemistry of DNA
Franklin had concluded that there were two outer sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior
Watson built a model in which the backbones were
antiparallel (their subunits run in opposite directions)
At first, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width
Instead, pairing a purine with a pyrimidine resulted in a uniform width consistent with the X-ray data
The relationship between structure and function is manifest in the double helix
Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material
Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication
In DNA replication, the parent molecule unwinds, and two new daughter strands are built based on base-pairing rules
Watson and Crick’s _____________ predicts that when a double helix replicates, each daughter molecule will have one old strand (derived or “conserved” from the parent molecule) and one newly made strand
semiconservative model of replication
Competing models were the conservative model
(the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new)
Experiments by Matthew Meselson and Franklin Stahl supported the semiconservative model
They labeled the nucleotides of the old strands with a heavy isotope of nitrogen, while any new nucleotides were labeled with a lighter isotope
The first replication produced a band of hybrid DNA, eliminating the conservative model
A second replication produced both light and hybrid DNA, eliminating the dispersive model and supporting the semiconservative model
The copying of DNA is remarkable in its speed and accuracy
More than a dozen enzymes and other proteins participate in DNA replication
Replication begins at particular sites called
—————————, where the two DNA strands are separated, opening up a replication “bubble”
origins of replication
A eukaryotic chromosome may have hundreds or even thousands of origins of replication
Replication proceeds in both directions from each origin, until the entire molecule is copied
At the end of each replication bubble is a replication fork, a Y-shaped region where
new DNA strands are elongating
Helicases are enzymes that untwist the double helix at the replication forks
Single-strand binding proteins bind to and stabilize single-stranded DNA
Topoisomerase corrects “overwinding” ahead of replication forks by breaking, swiveling, and rejoining DNA strands
DNA polymerases cannot initiate synthesis of a polynucleotide; they can only add nucleotides to an existing 3′ end
The initial nucleotide strand is a short RNA primer
An enzyme called
————– can start an RNA chain from scratch and adds RNA nucleotides one at a time using the parental DNA as a template
primase
The primer is short (5–10 nucleotides long), and
the 3′ end serves as the starting point for the new DNA strand
Enzymes called ____________ catalyze the elongation of new DNA at a replication fork
DNA polymerases
Most DNA polymerases require a primer and a DNA template strand
The rate of elongation is about 500 nucleotides per second in bacteria and 50 per second in human cells
Each nucleotide that is added to a growing DNA strand is a nucleoside triphosphate
dATP supplies adenine to DNA and is similar to the ATP of energy metabolism
The difference is in their sugars: dATP has deoxyribose while ATP has ribose
As each monomer of dATP joins the DNA strand, it loses two phosphate groups as a molecule of pyrophosphate
The antiparallel structure of the double helix affects replication
DNA polymerases add nucleotides only to the free 3′ end of a growing strand; therefore, a new DNA strand can elongate only in the 5′ to 3′ direction
Along one template strand of DNA, the DNA polymerase synthesizes a
————– continuously, moving toward the replication fork
leading strand
To elongate the other new strand, called
———————-, DNA polymerase must work in the direction away from the replication fork
the lagging strand
The lagging strand is
synthesized as a series of segments called Okazaki fragments, which are joined together by DNA ligase
DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
In mismatch repair of DNA, repair enzymes correct errors in base pairing
DNA can be damaged by exposure to harmful chemical or physical agents such as cigarette smoke and X-rays; it can also undergo spontaneous changes
In nucleotide excision repair, a nuclease cuts out and replaces damaged stretches of DNA
Error rate after proofreading repair is low but
not zero
Sequence changes may become permanent and can be passed on to the next generation These changes (mutations) are the source of the genetic variation upon which natural selection operates
Limitations of DNA polymerase create problems for the linear DNA of eukaryotic chromosomes
The usual replication machinery provides no way to complete the 5′ ends, so repeated rounds of replication produce shorter DNA molecules with uneven ends
This is not a problem for prokaryotes, most of which have circular chromosomes
Eukaryotic chromosomal DNA molecules have special nucleotide sequences at their ends called
telomeres
Telomeres do not prevent the shortening of DNA molecules, but they do postpone the erosion of genes near the ends of DNA molecules
It has been proposed that the shortening of telomeres is connected to aging
If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce
An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells
The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions
There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist
The bacterial chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein
Eukaryotic chromosomes have linear DNA molecules associated with a large amount
of protein
In a bacterium, the DNA is “supercoiled” and found in a region of the cell called the nucleoid
In the eukaryotic cell, DNA is precisely combined with proteins in a complex called chromatin
Chromosomes fit into the nucleus through an elaborate, multilevel system of packing
Most chromatin is loosely packed in the nucleus during interphase and condenses prior to mitosis
Loosely packed chromatin is called euchromatin
During interphase a few regions of chromatin (centromeres and telomeres) are highly condensed into heterochromatin
Dense packing of the heterochromatin makes it difficult for the cell to express genetic information coded in these regions
__________can undergo chemical modifications that result in changes in chromatin organization
Histones
