Download DNA and RNA Chapter 12 - local.brookings.k12.sd.us

DNA→RNA → PROTEINS
Chapters 16 & 17
http://faculty.uca.edu/~johnc/mbi1440.htm
http://www.wappingersschools.org/RCK/staff/teacherhp/johnson/visualvocab/mRNA.gif
Scientists originally thought PROTEINS
had to be the genetic material
1928- GRIFFITH’s EXPERIMENT
12 A
Images from: http://microvet.arizona.edu/Courses/vsc610/mic205/griffith.jpg
1943- EXPERIMENTS BY OSWALD AVERY,
MACLYN McCARTY, & COLIN MACLEOD
WITH LIPIDS,
POLYSACCHARIDES,
OR PROTEINS
THERE’S
NO TRANSFORMATION
ONLY NUCLEIC ACIDS
CHANGE THE BACTERIA
SO . . .
NUCLEIC ACIDS
CARRY THE
INFORMATION !
http://www.synapses.co.uk/genetics/dnastruc.html
http://oceanworld.tamu.edu/resources/oceanography-book/Images/BacteriophageCartoon.jpg
1952-Alfred Hershey and Martha Chase
Bacteriophages are viruses
that infect bacteria
Phages are made of
DNA surrounded
by a protein coat
http://www.mun.ca/biology/scarr/Chase_&_Hershey_1953.jpg
HERSHEY CHASE BLENDER EXPERIMENT
http://www.mun.ca/biology/scarr/hersheychase-experiment.jpg
ROSALIND FRANKLIN and MAURICE WILKINS
Analyzed DNA with X-ray crystallography to try
and determine structure of DNA
1953 - JAMES WATSON & FRANCIS CRICK
used Rosalind Franklin’s X-ray crystallography
images (PHOTO 51) to come up with alpha helix
model for the structure of DNA
http://en.wikipedia.org/wiki/Rosalind_Franklin
http://www.time.com/time/time100/scientist/profile/watsoncrick.html
DOUBLE HELIX
Linus Pauling's
Triple helix model
http://www.biosciences.bham.ac.uk/labs/minchin/tutorials/lgdna.html
Arrow from: http://www.harrythecat.com/graphics/b/arrow48d.gif
STRUCTURE OF NUCLEIC ACIDS
Built from
NUCLEOTIDE
SUBUNITS
NITROGEN BASES
CAN BE:
ADENINE
GUANINE
CYTOSINE
THYMINE
URACIL
Sugar can be DEOXYRIBOSE (DNA)
RIBOSE (RNA)
Image by: Riedell
DNA has no URACIL
RNA has no THYMINE
PURINES (A & G) have 2 RINGS
PYRIMIDINES (T, C, & U) have 1 RING
http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/DNA/DNA/fg4.html
http://student.ccbcmd.edu/~gkaiser/biotutorials/dna/fg29.html
Subunits come in as TRIPHOSPHATES
Splitting of nucleotide triphosphates
provides the energy to link the nucleotides
See animation
http://www.cat.cc.md.us/~gkaiser/biotutorials/energy/adpan.html
DNA
• DOUBLE STRANDED
• Strands run
ANTIPARALLEL
• Backbone =
sugars and phosphates
• Rungs of ladder =
nitrogen bases
• Hydrogen bonds hold sides
of ladder together
http://staff.jccc.net/pdecell/proteinsynthesis/antiparralell.gif
RNA
• SINGLE STRANDED
• Folds into 3D shape
• Backbone =
sugars and phosphates
• Rungs of ladder =
nitrogen bases
http://tigger.uic.edu/classes/phys/phys461/phys450/ANJUM04/
5’ and 3’ ENDS
• 5’ and 3’ ends named for the CARBON
Erwin Chargaff analyzed DNA from
different organisms and found
CHARGAFF’s RULES: A = T
G = C
Now know its because:
A always bonds with T
G always bonds with C
A Purine always bonds to a
Pyrimidine
SemiConservative
Conservative
Dispersive
MESELSON & STAHL
Images from: http://instruct1.cit.cornell.edu/courses/biog105/pages/demos/106/unit01/6.dnareplicationmodels.html
Grew bacteria for many generations in radioactive (heavy)
15N . . . so all DNA is heavy
Then grow in 14N, centrifuge as generations divide, and
check to see where heavy DNA ends up
http://www.sumanasinc.com/webcontent/animations/content/meselson.html
MESELSON & STAHL
Can tell which model
it is by the banding
patterns of DNA
molecules
SO WHAT ?
Proved
SEMI-CONSERVATIVE
REPLICATION MODEL
http://www.sumanasinc.com/webcontent/animations/content/meselson.html
Chromosome Structure in Prokaryotes
Approximately 5 million base pairs
3,000 genes
Chromosome
E. coli bacterium
Bases on the chromosome
DNA molecule in bacteria
single circular loop
© Pearson Education Inc, publishing as Pearson Prentice Hall. All rights reserved
CENTRAL DOGMA
OF MOLECULAR BIOLOGY
(How information passes in cells)
http://www.emunix.emich.edu/~rwinning/genetics/pics/dogma.jpg
http://student.ccbcmd.edu/~gkaiser/biotutorials/dna/fg12.html
Starting place =
ORIGIN OF REPLICATION
Bacteria have one
Eukaryotes-multiple spots
DNA
REPLICATION
FORK
HOW
NUCLEOTIDES
ARE ADDED
DURING DNA
REPLICATION
DNA
REPLICATION
FORK
http://bio.usuhs.mil/biochem4.html
TELOMERES & TELOMERASE
Each
replication
shortens
DNA strand
Primer removed but
can’t be replaced with
DNA because no
3’ end available for
DNA POLYMERASE
Image from: AP BIOLOGY by Campbell and Reese 7th edition
• TELOMERES-repetitive sequences
added to ends of genes to protect
information in code
• TELOMERASE can add to telomere
segments in cells that must divide
frequently
• Ex: Cells that give rise to sperm &
eggs
• Shortening of telomeres may play a
role in aging
• Cancer cells may have increased
telomerase activity which allows them
to keep dividing
ANIMATION
http://stemcells.nih.gov/info/scireport/appendixC.asp
PROOFREADING & REPAIR
• Mistakes in final DNA: 1 in 10 billion
• Mistakes in initial base pairing during replication:
1 in 100,000
• DNA POLYMERASE proofreads each base as it’s added
& fixes errors
• Errors can come from:
1. “proofreading mistakes” that are not caught
2. Environmental damage from CARCINOGENS
(Ex: X-rays, UV light, cigarette smoke, etc)
NUCLEOTIDE EXCISION REPAIR
• Cells continually monitor DNA and make repairs
• NUCLEASES-DNA cutting enzyme removes errors
• DNA POLYMERASE AND LIGASE can fill in gap and
repair using other strand
• Xeroderm pigmentosum- genetic disorder
– mutation in DNA enzymes that repair UV damage in skin cells
– can’t go out in sunlight
– increased skin cancers/cataracts
DNA →RNA
TRANSCRIPTION
RNA- the Other Nucleic Acid
Made of NUCLEOTIDES
Sugar = ribose
URACIL NOT THYMINE
Single stranded
http://tigger.uic.edu/classes/phys/phys461/phys450/ANJUM04
http://images2.clinicaltools.com/images/gene/dna_versus_rna_reversed.jpg
3 KINDS OF RNA HELP WITH INFO
TRANSFER FOR PROTEIN SYNTHESIS
RIBOSOMAL RNA (rRNA)
Made in nucleolus
2 subunits (large & small)
Combine with proteins to
form ribosomes
Bacterial ribosomes different
size than eukaryotic ribosomes
• Evidence for ENDOSYMBIOTIC THEORY
• Medically significant-some antibiotics target
bacterial ribosomes w/o harming host
rRNA and t-RNA images from Image from: Biology; Miller and Levine; Pearson Education publishing as Prentice Hall; 2006
mRNA image from http://wps.prenhall.com/wps/media/tmp/labeling/1140654_dyn.gif
3 KINDS OF RNA HELP WITH INFO
TRANSFER FOR PROTEIN SYNTHESIS
TRANSFER RNA (tRNA)
ANTICODON sequence
matches CODON on mRNA
to add correct
amino acids during
protein synthesis
AMINOACYL-tRNA SYNTHETASE
Enzyme attaches a specific
amino acid using energy from ATP
http://www-math.mit.edu/~lippert/18.417/lectures/01_Intro/
3 KINDS OF RNA HELP WITH INFO
TRANSFER FOR PROTEIN SYNTHESIS
MESSENGER RNA (mRNA)
carries code from DNA to ribosomes
TRANSCRIPTION
See a video clip about
TRANSCRIPTION
• Prokaryotes- mRNA functional as soon as
transcribed
• Eukarytoes-mRNA is processed before use
SEE PROCESSING VIDEO
Image from AP BIOLOBY by Campbell and Reese
mRNA’s require EDITING before use
• Message in NOT CONTINUOUS
• INTRONS are removed
Image by Riedell
mRNA EDITING
snRNPs (small nuclear ribonucleoproteins)
Made of proteins and RNA
Role in the SPLICEOSOME
(Complex that cuts out the
INTRONS and joins EXONS
to make the final mRNA)
RIBOZYMES-RNA molecules
that function as enzymes
(pre-RNA can remove its own introns)
INTRONS & EXONS
• PROTEIN DOMAINS
• Modular
• Ex:
– Active site,
– site to attach to membrane
• In many proteins, different
exons code for different
domains
• May facilitate evolution of
new proteins
(EXON SHUFFLING)
• Increased Crossing over
• Mix & match exons
Image from AP BIOLOGY by Campbell and Reese
GTP "cap" put on 5’ end- stability and used
to bind mRNA to ribosome
• PolyA "tail" put on 3’ end (AAA)- stability
and movement through the nuclear
membrane
Image from AP BIOLOBY by Campbell and Reese
TRANSLATION
(Protein synthesis)
Section 12-3
64 possible codons
Code is REDUNDANT
“WOBBLES”
Some amino acids
have more than one
codon.
START=AUG
(Methionine is 1st)
3 codons for STOP
Image from: Biology; Miller and Levine; Pearson Education publishing as Prentice Hall; 2006
http://www.biologycorner.com/bio4/notes/codon.html
Image from: Biology; Miller and Levine; Pearson Education publishing as Prentice Hall; 2006
Section 12-3
Translation
Figure 12–18 Translation (continued)
Section 12-3
Image from: Biology; Miller and Levine; Pearson Education publishing as Prentice Hall; 2006
TRANSLATION
How translation works
SEE ANOTHER
Translation Animation
REGULATION & MODIFICATION
DURING TRANSCRIPTION
• Proteins affect ability of RNA polymerase to bind to DNA
AFTER TRANSCRIPTION
• Speed of editing introns/exons
• access to transport proteins or speed of transport out
• Control amount of mRNA degradation by RIBONUCLEASES
DURING TRANSLATION
• Polyribosomes (polysomes)
• Availability of enzymes
• POST-TRANSLATIONAL MODIFICATION
• Alter protein (add phosphates, sugars, etc)
• Cut and join peptide chains
COMPLETING PROTEINS
• POLYRIBOSOMES (POLYSOMES)
– Numerous ribosomes translate same mRNA at
same time
– 3-D folding (1’, 2’, 3’ structure)
– Chaparonins
POST-TRANSLATIONAL MODIFICATIONS
– Some amino acids modified by addition of
sugars, lipids, phosphate groups, etc
– Enzymes can modify ends, cleave into pieces
join polypeptide strands (4’ structure)
Ex: Made as proinsulin
then cut
Final insulin hormone
made of two chains
connected by
disulfide bridges
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin.html
ARCHIBALD GARROD
1902
•
•
•
•
•
1st to suggest genes dictate phenotypes through enzymes that catalyze
specific chemical reactions
Postulated that the symptoms of an inherited disease are due to inability to
make a specific enzyme
Coined term “inborn errors of metabolism” to describe such diseases
Beginning of “One gene-one enzyme” hypothesis
ALCAPTONURIA- “black urine” disease- defect in enzyme that breaks down
amino acid tyrosine
http://www.personal.psu.edu/faculty/w/x/wxm15/Online/Molecular%20Biology/media/phenylalanine.gif
http://www.nature.com/bjp/journal/v147/n1s/images/0706466f5.jpg
Mutations
• Point mutations
– single base change
– base-pair substitution
• silent mutation
– no amino acid change
– redundancy in code
• missense
– change amino acid
• nonsense
– change to stop codon
Slide from Explore Biology by Kim Foglia
Point mutation leads to Sickle cell
anemia
What kind of mutation?
Slide from Explore Biology by Kim Foglia
Sickle cell anemia
Slide from Explore Biology by Kim Foglia
Mutations
• Frameshift
– shift in the reading
frame
• changes everything
“downstream”
– insertions
• adding base(s)
– deletions
• losing base(s)
– More damaging at
beginning of gene than
at end
Slide modified from: Explore Biology by Kim Foglia
XERODERMA PIGMENTOSUM
• UV light damage causes
THYMINE DIMERS
• Usually repaired
(Nucleotide Excision repair)
–
–
–
–
Repair enzymes defective
Increased skin cancer
severe burns in sunlight
Must avoid sunlight
AP BIOLOGY by Campbell and Reese
http://www.shadeshort.com/
REPLICATION
DNA → DNA ____________
TRANSCRIPTION
DNA → RNA ____________
RNA→ Protein TRANSLATION
___________