Download CHAPTER 16

Molecular Basis of
Inheritance
Chapter 16
DNA as Genetic Material
• Watson and Crick – 1st scientists to
propose structure of DNA responsible for transmission of
traits from 1 generation to next.
• Requires precise transmission
occurs.
http://www.ncbe.reading.ac.uk/DNA50/Resources/wc1993.gif
• Griffith - injected live bacterial
strains into mice.
• Mixed R strain of bacteria
(harmless) with heat-killed S strain
(harmful) and injected it.
• After mouse died, removed strain
from mouse.
• Transformation - change in
genotype and phenotype due to
assimilation of foreign substance
(now DNA) by cell.
• Substance found to be DNA supported by injecting bacteria into
viruses.
• Viruses consist of DNA (sometimes
RNA) enclosed by protective coat
of protein.
http://www.monografias.com/trabajos5/virus/Image164.gif
• To replicate - virus infects host
cell; takes over cell’s metabolic
machinery.
• Viruses that specifically attack
bacteria - bacteriophages (phages)
• Hershey and Chase labeled protein
and DNA - injected them into
bacteria.
http://www.swbic.org/products/clipart/images/bacteriophage.jpg
• Hershey and Chase concluded that
injected DNA of phage provides
genetic information that makes
infected cells produce new viral
DNA and proteins, which assemble
into new viruses.
• DNA doubles prior to mitosis.
• By 1940’s - discovered that DNA
was made of bases.
• Adenine, thymine, cytosine, and
guanine.
• Chargaff’s rules - an even amount
of thymine and adenine. (and
guanine and cytosine)
http://fig.cox.miami.edu/~cmallery/150/gene/BasePairing.gif
• Was known that sugar of one
nucleotide attached to phosphate
of another - forms backbone of
DNA.
• Watson 1st to figure out that DNA
was in helix shape + specific
distance between nucleotides.
• Partnered with Crick – came up with
double stranded model of DNA double helix.
Fig. 16.5
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Found that purine has to pair with
pyrimidine to achieve distance
needed.
• Knew that adenine always paired
with thymine and cytosine always
with guanine.
• Discovered that bases were held
together by hydrogen bonds.
• Adenine forms 2 hydrogen bonds
only with thymine; guanine forms 3
hydrogen bonds only with cytosine.
• Each gene found to have unique
sequence of nitrogen bases - DNA
strands not all the same.
http://academy.d20.co.edu/kadets/lundberg/dna_wallpaper/dna800x600.jpg
DNA Replication and Repair
• Watson and Crick discovered each
strand of DNA can make template
to make more DNA.
• Cell copies DNA - each strand
forms as template to determine
new complementary bases.
• Nucleotides pair in complementary
fashion, one by one.
• Happens by semiconservative
replication - each DNA molecule has
one parent strand and one daughter
strand.
• Idea later supported through
bacteria studies.
• This
• Even though process is amazingly
quick, only about 1 in a billion
nucleotides copied wrong.
• Proteins and enzymes also part of
process, not just nucleotides.
http://www.bio.miami.edu/dana/250/nucleotides.jpg
• Origins of replication - where
replication process begins.
• Bacteria - 1 site - replication looks
like bubble moving along DNA.
• Eukaryotes - many origins of
replication on each chromosome.
• Origin sites - DNA strands
separate forming replication
“bubble” with replication forks at
each end.
• Elongation of DNA catalyzed by
DNA polymerase.
• Polymerase adds complementary
bases to growing strand of new
DNA.
• Strands of DNA - antiparallel.
• Sugar-phosphate backbones run in
opposite directions.
• Each end of strand labeled either 5’
end or 3’ end.
• Nucleotides only be added to 3’
end.
• DNA strand can only elongate from
5’ end to 3’ end.
• Replication fork - problem - system
because strands run in opposite
directions (antiparallel)
http://www.mie.utoronto.ca/labs/lcdlab/biopic/fig/11.16.jpg
• 1 parent strand (leading strand -
one that runs 3’ to 5’) used as
template to keep complementary
strand continuous.
• Other strand (lagging strand - one
that runs 5’ to 3’) copied from fork
in small segments - Okazaki
fragments.
http://www.biology.arizona.edu/molecular_bio/problem_sets/nucleic_acids/graphics/repfork1.gif
• Fragments “glued” together by
DNA ligase to form backbone (made
of sugar and phosphate) of single
DNA strand.
• Polymerase adds nucleotides to
strands, cannot start whole
process.
• Done by a piece of RNA - primer.
• Primase links ribonucleotides that
are complementary to DNA
template into primer.
http://www.biologie.uni-hamburg.de/b-online/library/bio201/primase.jpg
• Once primer formed, polymerase
can add DNA nucleotides to growing
daughter strand of DNA.
• Later - different DNA polymerase
replaces original RNA with new
complementary DNA nucleotides there is no RNA left in strand.
• Helicase - untwists double helix of
DNA at replication fork.
• Single-strand binding proteins help
keep strands apart from one
another during replication.
• At replication fork, leading strand
copied continuously into fork from
single primer.
• Lagging strand copied away from
fork in short segments, each
requiring new primer.
• Original errors in reading of
template occur.
• Enzyme (DNA polymerase) removes
mistake and replaces it.
• Some things can alter DNA outside
of body.
http://library.thinkquest.org/C0123260/basic%20knowledge/images/basic%20knowledge/DNA/polymerase%201.jpg
• X-rays and UV rays can alter DNA
after replication.
• Mistakes can be fixed after DNA
synthesis because cell continually
monitors DNA.
• Mismatch repair, special enzymes
fix incorrectly paired nucleotides happens in certain types of cancers.
http://www.sinauer.com/cooper4e/sample/Figures/Chapter%2006/highres/CELL4e-Fig-06-24-0.jpg
• Nucleotide excision repair,
nuclease cuts out segment of
damaged strand.
• Xeroderma pigmentosa (genetic
disease) cannot go through process.
• Disease prevents person from going
in sun because UV rays interfere
with DNA replication.
• More susceptible to skin cancer
because they cannot fix mistakes.
http://162.129.70.33/images/xeroderma_pigmentosa_2_040620.jpg
• Limitations in DNA polymerase
create problems for linear DNA of
eukaryotic chromosomes.
• Ends of DNA strand can break
down from constant replication.
Fig. 16.18
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
• Ends of eukaryotic chromosomal
DNA molecules – telomeres special nucleotide sequences.
• Telomeres protect genes from
being eroded through multiple
rounds of DNA replication.
• When telomeres shorten,
telomerase uses piece of RNA to
lengthen telomere.
• Telomerase not present in all cells life span to certain tissues or
organism itself.
• Important for telomerase to be
present in gamete cells so they can
pass long telomeres on to zygote.
• Active telomerase in body cells can
be responsible for cancer cells
because cells keep dividing.