Nucleic Acids (Chapter 26)
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Transcript of Nucleic Acids (Chapter 26)
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Nucleic Acids (Chapter 26)
Composition of Nucleic Acids (26.2)
nucleic acids are polymers of nucleotides (called polynucleotides)
3 parts of a nucleotide
The Sugars
O
CH2
OH
NP
O
O
O
N
O
NH2
Monosaccharide (a sugar)
Heterocyclic nitrogen basePhosphate group
O
CH2 OH
OHOH
HO
O
CH2 OH
HOH
HO
D-ribose (in RNA) 2-Deoxy-D-ribose (in DNA)
Oxygen missing
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The Bases
N
N NH
N
NH2
H2N
HN
N NH
N
O
N
NH
NH2
O
H3CNH
NH
O
O
Sugar connects here
AdenineDNA, RNA
GuanineDNA, RNA
CytosineDNA, RNA
ThymineDNA
NH
NH
O
O
UracilRNA
purines pyrimidines
Sugar + Base = Nucleoside
O
CH2 OH
OHOH
HON
NNH
N
NH2
+
N
NN
N
NH2
O
OHOH
CH2
HO
Ribose Adenine Adenosine (a nucleoside)
Dehydration synthesis - loss of water Change names:AdenosineGuanosineThymidineCytidineUridine1’
2’3’
4’
5’
1
2
3
4
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8
9
1
2
345
6
6
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Sugar + Base + Phosphate = NucleotideBuilding blocks of nucleic acids - monomers of DNA and RNAnamed by adding 5’ monophosphate at the end of the nucleoside name.Adenosine 5’ monophosphate, guanosine 5’ monophosphate, etc
N
NN
N
NH2
O
OHOH
CH2
HO
N
NN
N
NH2
O
OHOH
CH2
OP
O
O
O
Adenosine (a nucleoside) Adenosine 5’-monophosphate (a nucleotide)
Ribonucleotide vs. deoxyribonucleotide
N
NN
N
NH2
O
OHOH
CH2
OP
O
O
O
N
NN
N
NH2
O
OH
CH2
OP
O
O
O
Ribonucleotide - contains riboseused for RNA
deoxyribonucleotide - contains deoxyriboseused for DNA
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Draw and name the 4 Nucleotides in DNA
-O
N
NN
N
NH2
O
HOH
HH
HH
OP
O-
O
O
H
HH
HH
N
N
NH2
O
OH
OP
O
O-
-O
O
HOH
HH
HH
HN
N
O
O
OP-O
O
O-
NH
N
N
O
NH2N
O
H
HH
HHOH
OP-O
O
O-
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Structure of Nucleic Acid Chains (26.3)nucleotides are linked together through phosphodiester linkages
bond between 3’ OH group of nucleotide and the phosphate of the next
OCH2
OH
OP- O
O
O-
N
OCH2
OH
OP- O
O
O-
N
OCH2OP-O
O
O-
N
OCH2
OH
OPO
O
O-
N
+
3’
5’
5’
3’
5’
3’Phosphodiester link
5’ end
3’ end
A dinucleotide
Note:
pg. 745 fig is wrong - the P is not dbl bond to the 3’ O
Note:
pg. 745 fig is wrong - the P is not dbl bond to the 3’ O
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The phosphates and sugars form the DNA backboneDNA sequences differ based on the order of the bases like protein sequence differs based on the order of the side chains
A DNA sequence is read from the 5’ to the 3’ end
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Draw the full structure of the trinucleotide C-A-T and label the 5’ and 3’ ends.Draw a box around each nucleotide.
O
H
HH
HH
N
N
NH2
O
OH
OP
O
O-
-O
-O
N
NN
N
NH2
O
HOH
HH
HH
OP
O-
O
O
HOH
HH
HH
HN
N
O
O
OP-O
O
O-
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Base Pairing in DNA (25.4)Chargaff’s Rules - %A = %T, %G = %C
DNA consists of 2 polynucleotide strands non-covalently interactingStrands wind around each other in a helical, screw-like fashion - called the double helixSugar-phosphate backbone is on outside, bases are on insideresembles a spiral staircase
The hydrophobic effect holds the 2 strands of DNA together - NOT H-BONDSH-bonds and ion-dipole interactions with cations and solvent add to stability
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Watson-Crick Base-PairingH-bonds are responsible for directing replication and transcriptionbase pairing is described as complementary. If T is on one strand, A is on the opposite.
2 H-bonds3 H-bonds
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Structure of duplex DNA2 Chains run antiparallel 3 types of duplex DNA1) B-DNA - right handed helix - most studied/common form in body
10 base pairs per turn2) A-DNA - right handed helix - found in low salt conditions
11 base pairs per turn3) Z-DNA - left-handed helix - found in nature - function unknown
occurs in high G/C areas
B-DNAwide major groove in B-DNA and narrow minor groove
many proteins such as DNA polymerase, RNA polymerasebind in the major groove
major
minor
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Organization of DNATotal number of base pairs in a human cell is 3 billionChromosome - molecule of DNA
In humans - 46 chromosomes - 23 pairs of chromosomeshorse - 64 chromosomes (32 pairs)cat has 38 (19 pairs)mosquito has 6 (3 pairs)If you straighten out all the DNA in a cell and line up end to end, there is about 2 metersof DNA in each cell
Gene - each chromosome is made up of thousands of genes - estimated there are~40,000 genes - codes for a protein
genetic code (26.9) - sequence of the bases specifies the sequence of amino acidsin a protein codon - base triplet that codes for an amino acid
insert codon table
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Replication of DNA (26.6)DNA double helix partially unwinds Bases are added based on the opposing strand as nucleoside triphosphatesDNA polymerase is the enzyme that copies DNA - it catalyzes the formation of the
phosphodiester bond between the 3’ OH and the 5’ phosphate on an incomingnucleoside triphosphate
New DNA is synthesized from the 5’ to the 3’ direction
New strand growing
OH attacks P
Bond breaks releasinga lot of energy
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Replication is semi-conservative
Each strand in the parent DNAacts as a template for the synthesisof a new DNA strand.
End up with 2 new identical DNA moleculeswith one parent strand per new moleculeand one new strand per new molecule
DNA always made in5’ to 3’ direction and strandsare always antiparellel
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Transcription of DNA (26.8)Transcription - synthesis of messenger RNA (mRNA) using DNA as a template
occurs in the nucleus, 1st step in protein synthesisDNA section to be transcribed is unwoundonly 1 strand of DNA is used as a template (template strand)the mRNA produced is complementary to the template strand butidentical to the non-template DNA strand (called the informational strand)
(except U for T and sugar)mRNA is produced from the 5’ to the 3’ end like in replicationpurpose of mRNA is to carry genetic information from DNA to cytosol
Example: Write the DNA complement (template strand) and the mRNA strandDNA strand (informational strand) 5’ ATG CCA GTA GGC CAC TTG TCA 3’DNA strand (template strand) 3’ TAC GGT CAT CCG GTG AAC AGT 5’mRNA 5’ AUG CCA GUA GGC CAC UUG UCA 3’
mRNA made is a complete copy from start to stop codonnot everything copied is used to make protein
Exons are in pink - expressed part of gene
intervening parts that donot code for protein
This is the mRNA that is used to makeprotein
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Translation of mRNA (26.10)Translation - synthesis of protein based on mRNA sequence
mRNA leaves nucleus - translation occurs in thecytoplasm on ribosomes
ribosome - scaffolding for translation - holds the mRNA, tRNA,and enzymes in place composed of rRNA and protein
t-RNA - each codon has a t-RNA with the corresponding amino acid covalently attachedanticodon is at base of t-RNA molecule and is complementary to codonon mRNA - the is responsible for bringing the correct amino acid to theribosome to add to the protein chain.
F in yellow
aa binds here
anticodon
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Genetic Mutations Point Mutations- a single base change
Normal DNA ATG-GAC-TTC
Mutant DNA ATG-CAC-TTC
Classified as:
transitions- flipping the base pair to complement DNA: G to C or A to T.(purine purine or pyrimidine pyrimidine)
transversions- switching base pairs: G/C to A/T.(purine pyrimidine or vice versa)
Is the above mutation a transition or transversion?
Point mutations may or may not affect transcription:
Missense mutations- a change that specifies a different AA. Ex. GUU GCU resulting in Val AlaBase substitution leads to AA substitution.May result in no phenotype, mild, or very serious consequences.Refer to pg. 757 table mRNA codon assignments of base triplets.
Normal DNA A T G - G G C - T T CRNA A U G – G G C – U U CAmino acid _Met_ - _Gly_ - _Phe_
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Nonsense mutations- a change that produces a stop codon resulting in a prematurely shortened protein.
ex. CGA UGA gives Arg stop-The effects are variable depending upon how much truncated protein is present and required for its function.
Normal DNA T T G - A A C - T A CRNA A A C - U U G - A U GAmino acid _Asn_ - _Leu_ - _Met_
Normal DNA T T G - A T C - T A CRNA A A C - U A G - A U G Amino acid _Asn_ - _stop_ - _Met_
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Silent mutationscauses a change that specifies the same AA. Ex. GUU GUC results in Val Val
How is that possible?(a) Often true in 3rd position of a codon, especially transitions. The change doesn’t
Modify the codon to produce a different AA ( single- nucleotide polymorphism (SNP) specifies The same AA.
(b) May terminate protein synthesis by introducing a stop codon.
the genetic code is degenerate
resultNormal DNA T T G - A T C - T A CRNA A A C - U A G - A T GAmino acid _Asn_ - _stop_ - _Met__
Normal DNA T T G - A T T - T A CRNA A A C - U A A - A T G Amino acid _Asn_ - _stop_ - _Met_
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Frameshift mutations- the number of the inserted or deleted basesNot in a multiple of 3, so that all triplets following the mutation are Read differently.
(a) this mutation changes all the AA downstream & very likely to create a nonfunctional product since it may differ greatly from normal protein.(b) reading frames other than the correct one often contain stop codons which will truncate the mutant protein prematurely.
Deletion Mutation* loss of one or more bases
Normal DNA A T G - G A C - T T C
Mutant DNA ATG – GCT- TC
Insertion Mutation* addition of one or more bases
Normal DNA A T G - G A C - T T C
Mutant DNA ATT - GGA – CTT- C
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Causes of Mutations
Can be the result of different events:
1) Spontaneous- occurs as a result of natural processes in the cell.
- naturally occurring mutagens in the environment- DNA replication errors
2) Mutagens- external agent that can cause a mutation (induced)
- error in base sequence that is carried along in DNA replication.
Carcinogens – cancer causing agents/ chemicals in the environment. ( contain polycyclic aromatic hydrocarbons
and amines)
Examples: lung cancer from chemicals in cigarettes
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Sunbathing damages DNAUV radiation does numerous things to DNA
1) Causes breaks in sugar phosphate backbone - DNA cannot replicate/transcribe- results in cell death
2) Causes “photodimers” - thymine dimers are most common - occurs btw adj T onsame strand
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Thymine dimers “kink” DNA
Undamaged DNA UV damaged DNAthymine dimer pulls thymines
closer together causing theDNA kink
The kink causes:1) replication/transcription to terminate at the point of the dimeror even worse,2) DNA polymerase iota will replicate through but misinserts T or G opposite one
of the thymines in the dimer instead of A and only 1 base is inserted opposite it.
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Cigarette smoke damages DNABenzo[a]pyrene is the main cancer causing agent in cigarette smokeBenzo[a]pyrene enters body and is converted to BPDE which covalently attaches
to DNA
This is your DNA This is your DNA on Cigarettes
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How does BPDE cause mutations?
p53 - tumor suppressor protein- scans DNA for damage during cell division- if damage is spotten, p53 stops cell division and activates DNA repair systems- if damage is too severe to be fixed, p53 triggers apoptosis (programmed cell
death)- over 50% of all cancers have a disabled p53- over 80% of all lung cancers have a disabled p53
BDPE is a potent mutagen of p53 by causing G:C to T:A transversions