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C16 (Many proteins work together in DNA replication and repair…
C16
Many proteins work together in DNA replication and repair
double helix
Where the relationship between structure and function is manifested
The Basic Principle: Base Pairing to a Template Strand
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 semiconservative model
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
Competing models were the conservative model (the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new)
DNA Replication
The copying of DNA is remarkable in its speed and accuracy
Replication begins at particular sites called origins of replication, where the two DNA strands are separated, opening up a replication “bubble”
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 relieves the strain of twisting of the double helix by breaking, swiveling, and rejoining DNA strands
Synthesizing a New DNA Strand
DNA polymerases require a primer to which they can add nucleotides
The initial nucleotide strand is a short RNA primer
This is synthesized by the enzyme primase
Enzymes called DNA polymerases catalyze the synthesis of new DNA at a replication fork
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
Antiparallel Elongation
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
affects replication
leading strand
moving toward the replication fork
lagging strand
DNA polymerase must work in the direction away from the replication fork
The lagging strand is synthesized as a series of segments called Okazaki fragments, which are joined together by DNA ligase
Proofreading and Repairing DNA
nucleotide excision repair
a nuclease cuts out and replaces damaged stretches of DNA
mismatch repair
repair enzymes correct errors in base pairing
DNA polymerases
proofread newly made DNA, replacing any incorrect nucleotides
The error rate after proofreading and 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 and are ultimately responsible for the appearance of new species
DNA is the genetic material
The role of DNA in heredity was first discovered by studying bacteria and the viruses that infect them
Frederick Griffith
worked with two strains of a bacterium, one pathogenic and one harmless
transformation
a change in genotype and phenotype due to assimilation of foreign DNA
Evidence That Viral DNA Can Program Cells
bacteriophages
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
Additional Evidence
evidence of diversity
In 1950, Erwin Chargaff reported that DNA composition varies from one species to the next
DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group
The nitrogenous bases can be adenine (A), thymine (T), guanine (G), or cytosine (C)
Chargaff’s rules
The base composition of DNA varies between species
In any species the number of A and T bases is equal and the number of G and C bases is equal
The basis for these rules was not understood until the discovery of the double helix
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
A chromosome consists of a DNA molecule packed together with proteins
Eukaryotic chromosomes
linear DNA molecules associated with a large amount of protein
DNA is precisely combined with proteins in a complex called chromatin
Proteins called histones are responsible for the first level of packing in chromatin
nucleosome
the basic unit of DNA packaging
especially their histone tails, are involved in the regulation of gene expression
bacterial chromosome
a double-stranded, circular DNA molecule associated with a small amount of protein
the DNA is “supercoiled” and found in a region of the cell called the nucleoid