211F06 Lecture Notes Molec Basisl Inheritance

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Principles of Biology Lecture Notes
Fall, 2006
MOLECULAR BASIS OF INHERITANCE
The Search for the Genetic Material
•The role of DNA in heredity first worked out by studying
Evidence That DNA Can Transform Bacteria
•Frederick Griffith - Streptococcus pneumoniae
–bacterium causes pneumonia in mammals
–a pathogenic strain & a nonpathogenic strain
Evidence That Viral DNA Can Program Cells
•Additional evidence for DNA as the genetic material
•heat-killed remains of pathogenic strain mixed with living cells of the nonpathogenic strain,
some living cells became pathogenic
•He called the phenomenon
•Now defined as a change in
• due to
The Hershey and Chase experiment
studying bacteriophages a virus that infects bacteria
widely used as tools by researchers in molecular genetics
Fig 16.4
Additional Evidence That DNA Is the Genetic Material
Prior to the 1950s, it was already known that DNA
Is a polymer of
, each consisting of
components:
Erwin Chargaff
DNA base composition
from one species to the next
molecular diversity among diverse species made DNA a more credible candidate for the genetic
material
Also found all species:
Challenge: How Does DNA Structure Produce Its Role in Inheritance?
Maurice Wilkins & Rosalind Franklin study molecular structure by
Franklin from her picture of DNA molecule concluded
• DNA =2 antiparallel sugar-phosphate backbones
• nitrogenous bases paired in the molecule’s interior
• specific base pairing: A-T& G-C
Watson and Crick:
Franklin’s X-ray crystallographic images of DNA
deduced that DNA was a double helix
Specific pairing dictated by the structure of the bases
Each base pair forms a different number of hydrogen bonds
A & T form 2 H bonds; C & G form 3 H bonds
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Complementary Base Pairing
A & T form
bonds
C & G form
bonds
Sugar =
“Function” of each C in the sugar:
C1 –
C4 C2 –
C5 –
C3 –
Complementary Base Pairing
•Is The Mechanism of Base Pairing to a Template Strand
•Since the two strands of DNA are complementary
–Each strand acts as a
for
•Occurs in both
–REPLICATION =
–TRANSCRIPTION =
NOTE: Strand = DNA Molecule
DNA Replication: - Overview
•In DNA replication
–The parent molecule
, and
new daughter strands are built
based
NOTE: molecule = DNA double helix
DNA Replication: : Semiconservative I
–Each of the two new daughter molecules will have
strand, derived from
–and one newly made strand
DNA Replication: : Semiconservative II
Conclusion from Meselson & Stahl experiment
Fig
Replication is
DNA Replication: : Semiconservative III
Experiments performed by Meselson and Stahl
Supported the
DNA Replication: Origins of Replication
•Replication begins at special sites called
–Eukaryotic chromosome –
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Fig:
:
model of DNA replication
, where the
of replication origins
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DNA Replication: Elongation
•Elongation of new DNA at a
–Is catalyzed by
, which add
to the
end of a growing strand
DNA Replication: Antiparallel Elongation
•Effect on replication of the antiparallel structure of the double helix
•DNA polymerases
Only adds nucleotides to free
end of a growing strand
•Along one template strand of DNA, the leading strand
DNA polymerase III can synthesize a complementary strand
, moving toward
•Along the other new strand of DNA, the lagging strand
DNA polymerase III must work in the direction
the replication fork
Lagging strand is synthesized as
then
, which are
by
DNA Replication: Leading Strand & Lagging Strand
•Synthesis of leading and lagging strands during DNA replication Fig:
DNA Replication: Priming DNA Synthesis
DNA polymerases cannot
the synthesis of a polynucleotide
They can only
The initial nucleotide strand is an
Only
primer is needed for synthesis of the leading strand
But for synthesis of the lagging strand,
must be primed
Fig
DNA Replication:
Other Proteins That Assist DNA Replication
Fig:
Helicase
Topoisomerase
single-strand binding protein
DNA Replication A summary
•
•
Fig
The DNA Replication Machine as a Stationary Complex
– The various proteins that participate in DNA replication
– Form a single large complex, a DNA replication “machine”
The DNA replication machine
– Is probably stationary during the replication process
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DNA Replication: Replicating the Ends of DNA Molecules
•The ends of eukaryotic chromosomal DNA get shorter with each round of replication
•Eukaryotic chromosomal DNA molecules
Have at their ends nucleotide sequences, called
that postpone the
erosion of genes near the ends of DNA molecules
DNA Replication: Replicating the Ends of DNA Molecules
•The ends of eukaryotic chromosomal DNA get shorter with each round of replication
•If the 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
DNA Replication: Proofreading and Repairing DNA
DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
In mismatch repair of DNA
Repair enzymes correct errors in base pairing
In nucleotide excision repair
Enzymes cut out and replace damaged stretches of DNA
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