06 Lec - Bio024 Nucleic Acid

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

● Deoxyribonucleic acid (DNA) is a nucleotide polymer in


OUTLINE which each of the monomers contains deoxyribose, a
phosphate group, and one of the heterocyclic bases
I. Introduction adenine, cytosine, guanine, or thymine.
II. Nucleic Acid ● Ribonucleic acid (RNA) a nucleotide polymer in which each
A. 2 Types of Nucleic Acids of the monomers contains ribose, a phosphate group, and
i. Deoxyribonucleic Acid (DNA) one of the heterocyclic bases adenine, cytosine, guanine,
ii. Ribonucleic Acid (RNA)
B. Nucleotide Building Blocks
or uracil
i. Pentose Sugar
ii. Nitrogenous Bases
iii. Phosphate
C. Nucleotide Formation
i. Information Concerning the Eight Nucleotides that
are Building Blocks for DNA and RNA
D. Primary Nucleic Acid Structure
III. DNA Double Heli
A. Forms of DNA double helix
B. Differences between the forms of DNA double helix
C. Prokaryotic and Eukaryotic DNA Molecules
IV. Supercoiling in Prokaryotic DNA at Tertiary Structure
V. Supercoiling in Eukaryotic DNA
A. Packaging of DNA (After Replication) James Dewey Watson & Francis
B. Prokaryotic Replication of DNA Molecules Crick
VI. Prokaryotic vs Eukaryotic Replication
A. Similarities Friedrich Miescher
B. Differences
C. The Eukaryotic Cell Cycle ‘’’
D. Antimetabolites: Anticancer Drugs that Inhibits DNA
synthesis
E. Types of RNA
F. Transcription: RNA Synthesis discovered nucleic Coined DNA molecule as
VII. The Genetic Code acids in 1869 while three-dimensional double helix
A. Two Features of the tRNA Structure are of Particular studying the nuclei of structure
Importance white blood cells
B. Antibiotic: Protein Synthesis Inhibitors
C. Mutations
i. Types of Mutation
ii. Gene or DNA Mutation FEATURES DNA RNA
D. Chromosome Mutation
Type of Strands Double helix w/ Single strand
anti-parallel &
INTRODUCTION complementary
● One of the striking aspects of natural order is the sense of strands
unity that exists between members of successive generations
in each species. Length of Strands Longer Shorter
● fttt
● Furthermore, cells contain all the instructions needed for Location Found in the Forms in the
making the complete organism of which they are a part. nucleus, with a nucleolus, and
● Hence, an almost totally stable bank of information must small amount also then moves to
always be preserved and passed from one generation to the present in specialized
next if individual species are to maintain their identities mitochondria. regions of the
relatively unchanged over millions of years. cytoplasm
● It is well established that this bank of genetic information, depending on the
within the cell, takes the form of a macromolecule, type of RNA
deoxyribonucleic acid (DNA), which serves as the carrier formed.
of genetic information in both prokaryotes and
eukaryotes. DNA exhibits a rare purity of function by being Primary Function Replicates and converts the
one of the few macromolecules known to perform, with only stores or the genetic information
minor exceptions, the same basic functions across species blueprint genetic contained within
barriers. information DNA to a format
NUCLEIC ACID used to build
● Nucleic Acid is an unbranched polymer containing the proteins
monomer units called nucleotides.
Important differences between DNA and RNA appear in Sugar Unit Deoxyribose Ribose
their secondary and tertiary structures (deoxygenated at
C2)
2 TYPES OF NUCLEIC ACIDS

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

NUCLEOTIDE BUILDING BLOCKS -monophosphate


PENTOSE SUGAR Uracil U Unidine Uridine 5’ UMP
-monophosphate

PRIMARY NUCLEIC ACID STRUCTURE

NITROGENOUS BASES

Purines “PurGA” DNA - A,G,C,T


Pyrimidine “PyCUT” RNA - A,G,C,U

PHOSPHATE

Phosphoric acid Hydrogen Phosphate ion

NUCLEOTIDE FORMATION
● Formation of Nucleoside = Sugar + Base
● Then, Nucleotide = Nucleoside + Phosphate

INFORMATION CONCERNING THE EIGHT NUCLEOTIDES Important points about nucleic acid structure:
THAT ARE BUILDING BLOCKS FOR DNA AND RNA ● Each nonterminal phosphate group of the sugar–phosphate
Base Abbrv Nucleoside Nucleotide Abbrv. backbone is bonded to two sugar molecules through a
3’(prime), 5’(prime)-phosphodiester linkage.
DNA
○ There is a phosphoester bond to the 5’ carbon of one
Adenine A Deoxyadenosine Deoxyadenosine 5’ dAMP
sugar unit and a phosphoester bond to the 3’ carbon of
-monophosphate
the other sugar.
Guanine G Deoxyguanosine Deoxyguanosine 5’ dGMP ● A nucleotide chain has directionality.
-monophosphate ○ One end of the nucleotide chain, the 5’ end, normally
Cytosine C Deoxycytidine Deoxycytidine 5’ dCMP carries a free phosphate group attached to the 5’
-monophosphate carbon atom.
Thymine T Deoxythymidine Deoxythymidine 5’ dTMP ○ The other end of the nucleotide chain, the 3’ end,
-monophosphate normally has a free hydroxyl group attached to the
RNA 3’ carbon atom.
Adenine A Adenosine Adenosine 5’ AMP ○ By convention, the sequence of bases of a nucleic acid
-monophosphate strand is read from the 5’ end to the 3’ end.
Guanine G Guanosine Guanosine 5’ GMP ● Each nonterminal phosphate group in the backbone of a
-monophosphate nucleic acid carries a -1 charge. The parent phosphoric acid
Cytosine C Cytidine Cytidine 5’ CMP molecule from which the phosphate was derived originally

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

had three -OH groups . Two of these become involved in the


3’,5’-phosphodiester linkage. The remaining -OH group is
free to exhibit acidic behavior— that is, to produce a H+ ion.
DNA DOUBLE HELIX

● Base Pair
A physical restriction, the size of the interior of the DNA
double helix, limits the base pairs that can
hydrogen-bond to one another.
○ Only pairs involving one small base (a pyrimidine) one
large base (a purine) correctly “fit” within the helix ● A-DNA a form of a DNA double helix characterized by
interior. having fewer residues per turn and major and
○ There is not enough room for two large purine bases to fit minor grooves with dimensions that are more
opposite each other (they overlap), and two small similar to each other than those of B-DNA. ‘
pyrimidine bases are too far apart to hydrogen bond to
one another effectively. Of the four possible Found as artifact of DNA preparation or
purine–pyrimidine combinations (A–T, A–C, G–T, and dehydrated B-DNA samples
G–C), hydrogen-bonding possibilities are most favorable
for the A–T (2 H-bond) and G–C (3 H-bond) pairings, and ● B-DNA the most common or principal form of the
these two combinations are the only two that normally DNA double helix that occurs in nature.
occur in DNA.
○ The pairing of A with T and that of G with C are said ● Z-DNA has been seen to occur naturally under certain
to be complementary. A and T are complementary circumstances.
bases, as are G and C.
○ The fact that complementary base pairing occurs in Has zigzag look of the phosphodiester backbone
DNA molecules explains, very simply, why the when viewed from the side
amounts of the bases A and T present are always
equal, as are the amounts of G and C. %A = 5 %T DIFFERENCES BETWEEN THE FORMS OF DNA DOUBLE
and %C 5 =%G HELIX
○ For example, human DNA contains 30% adenine, Chr

30% thymine, 20% guanine, and 20% cytosine. Features A-DNA B-DNA Z-DNA (Zigza)
○ The two strands of DNA in a double helix are not
identical—they are complementary. Helix turn Right handed Right handed Left handed
● Complementary DNA strands are strands of DNA in a it winds in the it winds in the it winds in the
double helix with base pairing such that each base is located direction of the direction of the direction of the
opposite its complementary base. fingers of the fingers of the fingers of the left
○ Wherever G occurs in one strand, there is a C in the right hand as the right hand as hand as the
other strand; wherever T occurs in one strand, there is an thumb is placed the thumb is thumb is placed
A in the other strand. However, with RNA the base A is upward placed upward upward
paired with U not with T.
● Hydrogen bond and Base stacking H-bond stabilizes Major grove Narrow and Wide and Deep Flat
double helix together with base stacking (like stack of coins). Deep
These stacking interactions are as important in their
stabilization effects as is the hydrogen bonding associated Minor grove Wide and Narrow and Narrow and deep
with base pairing—perhaps even more important. Purine and shallow deep
pyrimidine bases are hydrophobic in nature, so their
stacking interactions are those associated with hydrophobic Number of 11 10 12
molecules—mainly London forces. base pairs
per helical
Forms of DNA double helix (Campbell 8th ed.) turn
Present In DNA-RNA Chromosomal In sequence of
mostly hybrids or DNA alternating
RNA-RNA purines and
double stranded pyrimidines (ex.
regions polyGC like
dCpGpCpGpCp
G)
PROKARYOTIC AND EUKARYOTIC DNA MOLECULES
PROKARYOTIC EUKARYOTIC PROKARYOTIC EUKARYOTIC
DNA DNA DNA DNA

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

● 2 TYPES OF TOPOISOMERASE
DNA is found DNA is found Small amount of More DNA
in the in the nucleus DNA in the form of a arranged in ○ Class I topoisomerases - cut the phosphodiester
cytoplasm of of the cell, single, Circular multiple, backbone of one strand of DNA, pass the other end
prokaryotic inside the chromosomes linear through, and then reseal the backbone.
cells & chloroplast & chromosome ○ Class II topoisomerase - cut both strands of DNA,
circular mitochondria s pass some of the remaining DNA helix between the
plasmids. Not cut ends, and then reseal.
found inside ● DNA gyrase- is a bacterial topoisomerase that introduces
the organelles
negative supercoils into DNA.

Consist of 1 Consist of Introns are Introns are


copy of more than 1 absent present
genome copy of
genome

Contains of Contains of DNA replication DNA


small number large number occurs in the replication
of genes of genes cytoplasm occurs in the
nucleus

Organized into Organized into Chromosome Chromosome


single many contains single contains
chromosome chromosome origin of many origin
s s replication of replication

Not packed Packed with DNA replication DNA


with histones histones to is rapid replication is ● Left-handed (counterclockwise) twist. Analogous to
and form slow negative supercoil in right-handed helix such as B-DNA
condenses to chromatin ● Right-handed (clockwise) twist. Analogous to positive
form nucleoid supercoil in right-handed helix such as B-DNA

● Each chromosome in the nucleus of a eukaryote contains


one long, linear molecule of dsDNA, which is bound to a
complex mixture of proteins (histone and non-histone) to
form chromatin.
○ Eukaryotes have closed, circular DNA molecules in their
mitochondria, as do plant chloroplasts.
○ A prokaryotic organism typically contains a single,
double-stranded, supercoiled, circular chromosome.
○ Each prokaryotic chromosome is associated with
non-histone proteins that can condense the DNA to form a
nucleoid.
○ In addition, most species of bacteria (prokaryotes) also
contain small, circular, extrachromosomal DNA molecules
called plasmids.
○ Plasmid DNA carries genetic information, and undergoes
replication that may or may not be synchronized to
chromosomal division.
● Plasmids may carry genes that convey antibiotic resistance to
the host bacterium, and may facilitate the transfer of genetic
information from one bacterium to another
● Supercoiled DNA topology. The DNA double helix can
SUPERCOILING IN PROKARYOTIC DNA at be approximated as a two-stranded, right-handed coiled
rope. If one end of the rope is rotated
TERTIARY STRUCTURE counterclockwise, the strands begin to separate
● Prokaryotic DNA is circular, and this DNA forms supercoils. (negative supercoiling). If the rope is twisted clockwise
○ If the strands are underwound they form negative (in a right-handed fashion), the rope becomes
supercoils. overwound (positive supercoiling). Get a piece of
○ If they are overwound they form positive supercoils. right-handed multi strand rope, and carry out these
○ Underwound duplex DNA has fewer than the normal operations to convince yourself.
number of turns, whereas overwound DNA has more.
○ DNA supercoiling is analogous twisting or untwisting a
rope so that it is torsionally stressed.
○ Negative supercoiling introduces a torsional stress that
favors unwinding of the right handed B-DNA double helix,
whereas positive supercoiling overwinds such a helix.
○ Naturally occurring circular DNA is negatively supercoiled SUPERCOILING IN EUKARYOTIC DNA
except during replication, when it becomes positively ● The supercoiling of the nuclear DNA of eukaryotes (such
supercoiled. as plants, fungi and animals) is more complicated than the
supercoiling of the circular DNA from prokaryotes.
● TOPOISOMERASE Enzymes that are involved in
changing the supercoiled state of DNA

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

○ Eukaryotic DNA is complexed with a number of proteins,


especially with basic proteins that have abundant
positively charged side chains at physiological (neutral)
pH.
○ Electrostatic attraction between the negatively charged
phosphate groups on the DNA and the positively charged
groups on the proteins favors the formation of complexes
of this sort
○ The resulting material is called chromatin. Thus,
topological changes induced by supercoiling must be
accommodated by the histone protein component of
chromatin
● The principal proteins in chromatin are the histones, of which
there are five main types, called H1, H2A, H2B, H3, and H4.
All these proteins contain large numbers of basic amino acid Telomere: complexes of DNA plus proteins (collectively known as
residues, such as lysine and arginine. In the chromatin shelterin) located at the end s of. linear chromosomes. Used to
structure, the DNA is tightly bound to all the types of histone maintain structural integrity that protect the chromosomes
except H1.
● In electron micrographs, chromatin resembles beads on a CENTRAL DOGMA
string (Figure 9.16). This appearance reflects the molecular
composition of the protein–DNA complex. Each “bead” is a
nucleosome, consisting of DNA wrapped around a histone
core.

The Structure of chromatin. DNA is associated with histones in


an arrangement that gives the appearance of beads on a string.
The “string” is DNA, and each of the “beads” (nucleosomes)
consists of DNA wrapped around a protein core of eight
histone molecules. Further coiling of the DNA spacer regions
produces the compact form of chromatin found in the cell.

REVERSE TRANSCRIPTASE known as RNA-directed DNA


polymerase. Used by retroviruses for reverse transcription.

● chromatin a complex of DNA


and protein found in
eukaryotic nuclei
● histones basic proteins
found complexed to
eukaryotic DNA
● nucleosome a globular
structure in chromatin in
which DNA is wrapped
around an aggregate of
histone molecules

PACKAGING OF DNA (after replication) PROKARYOTIC REPLICATION OF DNA MOLECULES


● DNA replication is the biochemical process by which DNA
● Chromosomes is an individual DNA molecule bound to a
molecules produce exact duplicates of themselves.
group of proteins. Typically 15% by mass DNA and 85% by
mass proteins (Lippincott, 7th ed)

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

In DNA replication, the two strands of the DNA double helix


unwind, with the separated strands serving as templates for DNA Helicase influences the unwinding of DNA
the formation of new DNA strands. Free nucleotides pair with double helix, and the hydrogen bonds
the complementary bases on the separated strands of DNA. This between complementary bases are broken
process ultimately results in the complete.
DNA Polymerase verifies that the base pairing is correct
III and then catalyzes the formation of a
new phosphodiester linkage between
the nucleotide and the growing strand.

Also, recognizes the RNA primer & begins


to extend it with DNA.

Primase Synthesizes a short stretches of RNA


(~10 nucleotides long) that are completely
complementary and antiparallel to the
DNA template

DNA Ligase connect two strands of DNA together


by forming a bond between the
phosphate group of one strand
Replication Fork The point at which the DNA double (synthesized by DNA pol III) and the
helix is unwinding, which is constantly deoxyribose group on another(made by
changing (moving) DNA pol I) .

Okazaki Fragments short segments, (after their discoverer, It is used in cells to join together the
Reiji Okazaki), as the DNA unwinds Okazaki fragments which are formed
on the lagging strand
Nicks The breaks or gaps in the daughter
strand RNA Primer is RNA that prime (lay down short
strand of ribonucleotide) and initiates
Leading Strand The strand that grows continuously DNA synthesis.
○ Note: DNA primer is used for PCR
Lagging Strand The strand that is synthesized in small (polymerase chain reaction)
segments amplification while RNA primer is the
main ingredient of replication.
○ DNA POLYMERASE I -- excise
(removes) RNA primers from
fragments and replace the required
nucleotides.

PROKARYOTIC vs EUKARYOTIC REPLICATION


SIMILARITIES
● The steps for DNA replication are generally the same for all
prokaryotic and eukaryotic organisms. Unwinding the DNA is
accomplished by an enzyme named DNA helicase.
Manufacturing new DNA strands is orchestrated by
enzymes called polymerases.
● Both types of organisms also follow a pattern called
semi-conservative replication. In this pattern, the individual
strands of DNA are manufactured in different directions,
producing a leading and a lagging strand. Lagging

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

strands are created by the production of small DNA


fragments called Okazaki fragments that are eventually
joined together. Both types of organisms also begin new DNA
strands with a small primer of RNA.

DIFFERENCES
PROKARYOTIC EUKARYOTIC

It occurs in the cytoplasm It occurs inside the nucleus

There is a single origin of Origin of replication are


replication numerous or multiple
ANTIMETABOLITES: ANTICANCER DRUGS THAT INHIBITS
Replication occurs in 2 Uses unidirectional DNA SYNTHESIS
opposing ends replication ● Cancer is a disease characterized by rapid uncontrolled
cell division. Rapid cell division necessitates the synthesis of
Possess one or 2 types of Has 4 or more polymerase large amounts of DNA, as DNA must be present in each new
polymerase (ex. DNA polymerase γ cell produced. Numerous anticancer drugs are now available
replicates mitochondrial DNA) that block
● DNA synthesis and therefore decrease the rate at which new
cancer cells are produced. Antimetabolites are a class of
DNA polymerase III carries Initiation is carried out by
anticancer drugs that interfere with DNA replication
out both initiation and DNA polymerase α while
because their structures are similar to molecules required
elongation elongation by DNA
for normal DNA replication.
polymerase δ (lagging
● The structural similarity is close enough that enzymes
strand) and ε (leading
can be “tricked” into using the drug rather than the real
strand)
substrate needed. This “trickery” shuts down DNA synthesis,
which causes cells to die.
DNA repair and gap filling are DNA repair and gap filling are
● Four examples of commonly used antimetabolites and the
done by DNA polymerase I performed by DNA
molecules they “mimic” are as follows:
polymerase β.

Okazaki fragments are Okazaki fragments are


large, 1000-2000 nucleotides short, 100-200 nucleotides
long long

Replication is very rapid , Replication is slow, some


some 2000 base pair per 100 nucleotides per second.
second . Like bacteria Animal cells like human at
replication occurs at 40 mins 400hrs. ● Methotrexate:
It is a structural analog
DNA gyrase is needed. DNA gyrase is not needed. of folic acid (folate). A
But also have a distinct derivative of folic acid is
process for replicating the needed in one of the
telomeres at the ends of their early steps of nucleotide
chromosomes synthesis. Methotrexate
inhibits the conversion
With their circular only undergo DNA of folic acid to this
chromosomes, they have no replication during the needed derivative,
ends to synthesize and with S-phase of the cell cycle. which shuts down DNA
short replication, it occurs synthesis.
almost continuously.
● PROTEIN SYNTHESIS: The genetic master plan of an
organism is contained in the sequence of
The eukaryotic cell cycle deoxyribonucleotides in its deoxyribonucleic acid (DNA).
● The events surrounding eukaryotic DNA replication and However, it is through the ribonucleic acid (RNA)—the
cell division (mitosis) are coordinated to produce the cell “working copies” of the DNA— that the master plan is
cycle (Figure 29.21). The period preceding replication is expressed through transcription and then further
called the G1 phase (Gap1). DNA replication occurs translated.
during the S (synthesis) phase. Following DNA synthesis, ● RIBONUCLEIC ACID In addition to sugar unit, strand
there is another period (G2 phase, or Gap2) before difference and replacement of the base thymine with
mitosis (M). Cells that have stopped dividing, such as uracil for RNA, unlike DNA, RNA does not contain
mature neurons, are said to have gone out of the cell equal amounts of specific bases and molecules are
cycle into the G0 phase. Cells can leave the G0 phase much smaller than DNA molecules, ranging from 75
and reenter the early G1 phase to resume division. nucleotides to a few thousand nucleotides.

TYPES OF RNA (Refer to the central dogma for the location of


synthesis)

RNA Definition

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

Heterogenous nuclear RNA formed directly by DNA


(hnRNA) transcription.
Post-transcription processing
converts the heterogeneous
nuclear RNA to messenger
RNA

Small nuclear RNA (snRNA) facilitates the conversion of


heterogeneous nuclear RNA
to messenger RNA. It
contains from 100 to 200
nucleotides.

Messenger RNA (mRNA) carries instructions for


protein synthesis (genetic Note: The RNA produced from a gene through transcription is
information) to the sites for hnRNA, the precursor for mRNA
protein synthesis.
Post-Transcription Processing: Conversion of hnRNA to
Ribosomal RNA (rRNA) combines with specific mRNA
proteins to form ribosomes,
the physical sites for
protein synthesis. Most
abundant type of RNA in a
cell (75% to 80% by mass).

Transfer RNA (tRNA) delivers amino acids to the


sites for protein synthesis.
Are the smallest of the RNAs,
possessing only 75–90
nucleotide units.

TRANSCRIPTION: RNA Synthesis


● Transcription is the process by which DNA directs the Note: It is now known that not all bases in a gene convey genetic
synthesis of hnRNA/mRNA molecules that carry the coded information. Instead, a gene is segmented; both the introns and
information needed for protein synthesis. Messenger RNA exons of a gene are transcribed in the production of hnRNA.
production via transcription is actually a “two-step” process
in which an hnRNA molecule is initially produced and then is Figure 22.17 Heterogeneous
“edited” to yield the desired mRNA molecule. The mRNA nuclear RNA contains exons
molecule so produced then functions as the carrier of the and introns. Messenger RNA
information needed to direct protein synthesis. is heterogeneous nuclear
● A short segment of a DNA strand so transcribed, which RNA from which the introns
contains instructions for the formation of a particular have been excised.
hnRNA/mRNA, is called a gene. A gene is a segment of a
DNA strand that contains the base sequence for the
production of a specific hnRNA/mRNA molecule
Figure 22.18 An hnRNA
● In humans, most genes are composed of 1000–3500 molecule containing four
nucleotide units. Hundreds of genes can exist along a DNA exons, two of which (B and C)
strand. Obtaining information concerning the total number of are alternative exons, can be
genes and the total number of nucleotide base pairs present spliced in four different ways,
in human DNA has been an area of intense research activity producing for different
for the last two decades. A genome is all of the genetic proteins. Proteins can be
material (the total DNA) contained in the chromosomes of an produced with neither, either,
or both of the alternative
organism.
exons present.

● SPLICING - is the process of removing introns from an


hnRNA molecule and joining the remaining exons together to
form an mRNA molecule.
● snRNPs (Small nuclear ribonucleoprotein particle ) “snrnps” -
is the process of removing introns from an hnRNA
molecule and joining the remaining exons together to form an
mRNA molecule.
● SPLICEOSOMES - s a large assembly of snRNA molecules
and proteins involved in the conversion of hnRNA molecules
to mRNA molecules.

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[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

● ALTERNATIVE SPLICING - is a process by which several particular tRNA and facilitates its bonding to the tRNA.
different proteins that are variations of a basic structural motif
can be produced from a single gene ● The loop opposite the open end of the cloverleaf is the site for a
sequence of three bases called an anticodon. An anticodon is a
● TRANSCRIPTOME - is all of the mRNA molecules that can
three nucleotide sequence on a tRNA molecule that is complementary
be generated from the genetic material in a genome to a codon on an mRNA molecule. And, the ability of certain
anticodons to pair with codons that differ at the third base is called a
THE GENETIC CODE wobble.
● The genetic code is the assignment of the 64 mRNA codons
to specific amino acids (or stop signals). Ribosomes, which contain both
● A codon is a three nucleotide sequence in an mRNA rRNA and protein, have
molecule that codes for a specific amino acid. There were 61 structures that contain two
subunits. One subunit is much
of the 64 codons formed by various combinations of the bases
larger than the other.
A, C, G, and U were related to specific amino acids; the other
three combinations were termination codons (“stop” signals) ● P site or peptidyl site
for protein synthesis. ● A site or aminoacyl site
● The genetic code table was known: to be highly degenerate, ● Translocation – part of
that is, many amino acids are designated by more than one translation where the
codon except Met and Trp, which have only a single codon; ribosome moves down an
there is a pattern to the arrangement of synonyms; it is almost mRNA molecule three base position (codon) so that a new occupy the
ribosomal subunit.
universal; and an initiation codon exists (AUG for Met) and
existence of “stop” codons (UAG, UAA, and UGA).
ANTICODON and tRNA molecules

The amino acids used in protein synthesis do not directly


interact with the codons of an mRNA molecule. Instead, tRNA
molecules function as intermediaries that deliver amino acids to
the mRNA. At least one type of tRNA (cloverleaf shape) molecule
exists for each of the 20 amino acids found in proteins. ANTIBIOTIC: PROTEIN SYNTHESIS INHIBITORS
● In both cases, ribosomes are the sites for protein synthesis. Human
ribosomes are much larger than bacterial ribosomes..
● In bacteria, the initiator codon is N-formylmethionine.
● In human cells, it is methionine.
● In bacteria, mRNA translation begins while the mRNA is still being
transcribed from DNA. In human cells, mRNA translation begins only
after transcription.
● Bacteria/mRNAs undergo very little processing after being
transcribed and are very short-lived. In some cases, degradation of
mRNA begins before completion of transcription. In human cells,
transcribed mRNA (hnRNA) undergoes considerable processing
before mature RNA is formed.

Erythromycin: binds to the larger bacterial ribosome


subunit, blocking the exit of a growing
TWO FEATURES OF THE tRNA STRUCTURE ARE OF peptide chain
PARTICULAR IMPORTANCE: Terramycin blocks the A-site location on the ribosome,
● The 3’ end of the open part of the preventing the attachment of aminoacid
cloverleaf structure is where an amino
carrying tRNAs.
acid becomes covalently bonded to the
tRNA molecule through an ester bond. Streptomycin binds to the smaller bacterial ribosome
Each of the different tRNA molecules is subunit causing a shape change, which in
specifically recognized by an aminoacyl turn causes a misreading of mRNA
tRNA synthetase enzyme. These information
enzymes also recognize the one kind of
amino acid that “belongs” with the

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Neomycin binds to the smaller bacterial ribosome


subunit in a manner similar to When a base substitution results in a stop codon ultimately truncating
streptomycin. translation and most likely leading to a nonfunctional protein. Ex. Lys
Chloramphenicol binds to the ribosome and interferes with (AAG) to UAG (stop codon)
the formation of peptide bonds between
amino acids
MISSENSE CONSERVARTIVE NONCONSERVARTIVE
Mutation MUTATION MISSENSE MISSENSE
● Mutation is an error in base sequence in a gene that is
reproduced during DNA replication. Such errors alter the This type of mutation Result in an amino Result in an amino acid
is a change in one acid change. change that has different
genetic information that is passed on during transcription. DNA base pair that However, the properties than the wild
The altered information can cause changes in amino acid results in the properties of the type. The protein may
sequence during protein synthesis. A mutagen is a substitution of one amino acid remain lose its function, which
substance or agent that causes a change in the structure amino acid for the same Ex. Lys can result in a disease in
of a gene. Ex. Ultraviolet light another in the (polar basic) to Arg the organism. Ex. Lys
protein made by a (polar basic (polar basic) to Thr (Polar
TYPES OF MUTATION gene. neutral)
Note: there are a lot of class and type of mutation, however, we b. Frameshift mutation a mutation that inserts or deletes a base in
will only focus on the following examples. a molecule base sequence. This type of mutation occurs when
the addition or loss of DNA bases changes a gene's reading
frame. A reading frame consists of groups of 3 bases that each
GENE or DNA MUTATION CHROMOSOME MUTATION
code for one amino acid. A frameshift mutation shifts the
is a permanent alteration in the are alterations that affect whole
grouping of these bases and changes the code for amino acids.
DNA sequence that makes up a chromosomes and whole genes
The resulting protein is usually nonfunctional. Ex. Insertion and
gene rather than just individual
deletion
nucleotides

● Point mutation ● Inversion INSERTION


● Substitution ● Deletion One or more extra nucleotides
○ Silent ● Duplication are inserted or added into the
○ Nonsense ● Translocation replicating DNA, often resulting
○ Missense in frameshift. As a result, the
○ Conservative protein made by the gene may
○ Nonconservative not function properly
● Frameshift mutation
○ Insertion
○ Deletion

GENE or DNA Mutation


DELETION
A. Point mutation is a mutation in which one base in a DNA base Changes the number of DNA
sequence is replaced with another base. bases by removing a piece of
a. Substitution - One base is incorrectly added during replication DNA. Small deletions may
and replaces the pair in the corresponding position on the remove one or a few base pairs
complementary strand within a gene, while larger
deletions can remove an entire
gene or several neighboring
genes. The deleted DNA may
alter the function of the resulting
protein(s)

SILENT MUTATION
code for the same amino acid (a "synonymous substitution"). A silent CHROMOSOME MUTATION
mutation does not affect the functioning of the protein. A single nucleotide
can change, but the new codon specifies the same amino acid, resulting in
an unmutated protein.

This type of change is called synonymous change since the old and new
codon code for the same amino acid. Ex. Lys to Ly

NONSENSE MUTATION

ALER | CHUA | DELA CRUZ | DELOS REYES | EDICA | ESPINOSA 10


[LEC TRANS] P2 MODULE 6: NUCLEIC ACID

Chromosome A segment from A segment from A segment of a


Segment lost chromosome is one chromosome
transferred to chromosome is arm is inverted
another transferred to its
homologous
chromosome,
giving it a
duplicate of
some genes.

● Deletion - A region of a chromosome is lost, resulting in


the absence of all the genes in that area
● Translocation - A region from one chromosome is
aberrantly attached to another chromosome
● Duplication - A region of a chromosome is repeated,
resulting in an increase in dosage from the genes in that
region
● Inversion - One region of a chromosome is flipped and
reinserted

ALER | CHUA | DELA CRUZ | DELOS REYES | EDICA | ESPINOSA 11

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