LEARNING TARGETS:

MODULE 13 At the end of the module, students will be able to:

• Describe central dogma.
NUCLEIC ACID • Describe DNA replication, including the functions of DNA gyrase, DNA ligase, and DNA
polymerase; and,
(CENTRAL DOGMA) • Describe protein synthesis, including transcription and translation.

CENTAL DOGMA OF LIFE

The central dogma of molecular biology is a theory stating that genetic information flows only in one
direction, from DNA, to RNA, to protein, or RNA directly to protein.
I. DNA REPLICATION (DNA → DNA)
II. TRANSCRIPTION (DNA → RNA)
III. TRANSLATION (RNA → PROTEIN)

DNA REPLICATION
DNA replication is the process by which the genome’s DNA is copied in cells. Before a cell divides, it
must first copy (or replicate) its entire genome so that each resulting daughter cell ends up with its
own complete genome.

LEADING STRAND The strand is replicated continuously.

LAGGING STRAND The strand is replicated discontinuously.
DNA HELICASE Unwind and separate two strands of DNA
SINGLE STRANDED BINDING PROTEIN Prevent reannealing of parent strands
TOPOISOMERASE/DNA GYRASE Removes supercoiling
DNA PRIMASE Catalyze synthesis of RNA Primer
RNA PRIMER Allows DNA Polymerase to add new nucleotides
DNA POLYMERASE III Catalyzes elongation of DNA chains
OKAZAKI FRAGMENTS The short lengths of DNA that are produced by the
discontinuous replication of the lagging strand
DNA POLYMERASE I Removes the RNA primer and replaces it with DNA
nucleotides
DNA LIGASE Nucleotides have matching ends, ligase can link
them to form a single, unbroken molecule of DNA
INHIBITORS OF DNA REPLICATION
• Quinolones and Fluoroquinolones: inhibit DNA gyrase (prokaryotic topoisomerase II),
preventing DNA replication and transcription.

TRANSCRIPTION
Transcription is the synthesis of a complementary strand of RNA from a DNA template which takes
place inside the nucleus.
During transcription, a strand of mRNA is synthesized using a specific portion of the cell’s DNA as a
template. In other words, the genetic information stored in the sequence of nucleobases of DNA is
rewritten so that the same information appears in the base sequence of mRNA.
As in DNA replication, a guanine (G) in the DNA template dictates a cytosine (C) in the mRNA being
made, and a C in the DNA template dictates a G in the mRNA. Likewise, a thymine (T) in the DNA
template dictates an adenine (A) in the mRNA. However, an adenine in the DNA template dictates an
uracil (U) in the mRNA, because RNA contains uracil instead of thymine. If, for example, the
template portion of DNA has the base sequence ATGCAT, the newly synthesized mRNA strand will
have the complementary base sequence UACGUA.
STEPS OF TRANSCRIPTION
• Initiation is the beginning of transcription. It occurs when the enzyme RNA polymerase binds
to a region of a gene called the promoter. This signals the DNA to unwind so the enzyme can
‘‘read’’ the bases in one of the DNA strands. The enzyme is now ready to make a strand of
mRNA with a complementary sequence of bases.
• Elongation is the addition of nucleotides to the mRNA strand. RNA polymerase reads the
unwound DNA strand and builds the mRNA molecule, using complementary base pairs.
• Termination is the ending of transcription and occurs when RNA polymerase crosses a stop
(terminator) sequence in the gene. The mRNA strand is complete, and it detaches from DNA.

PROMOTER REGION RNA polymerase begins to transcribe a gene

RNA POLYMERASE Synthesizes RNA molecules from a template of DNA
TERMINATOR REGION The point where transcription stops
mRNA Product of DNA Transcription and is necessary for protein
synthesis

INHIBITORS OF RNA SYNTHESIS

• Actinomycin D and Mitomycin: intercalate with DNA strands, thus blocking
transcription. They are used as anticancer drugs. 2.
• Rifampicin is widely used in the treatment of tuberculosis and leprosy.

DNA TRANSLATION
During translation, codons of an mRNA are “read” sequentially; and, in response to each codon, the
appropriate amino acid is assembled into a growing chain. The site of translation is the ribosome,
and transfer RNA (tRNA) molecules both recognize the specific codons and transport the required
amino acids. Each tRNA molecule has an anticodon, a sequence of three bases that is
complementary to a codon. In this way, a tRNA molecule can base-pair with its associated codon.
Each tRNA can also carry on its other end the amino acid encoded by the codon that the tRNA
recognizes. The functions of the ribosome are to direct the orderly binding of tRNAs to codons and to
assemble the amino acids brought there into a chain, ultimately producing a protein. The two
ribosomal subunits, a tRNA with the anticodon UAC, and the mRNA molecule to be translated,
along with several additional protein factors, all assemble. This sets up the start codon (AUG) in the
proper position to allow translation to begin. After the ribosome joins the first two amino acids with a
peptide bond, the first tRNA molecule leaves the ribosome. The ribosome then moves along the
mRNA to the next codon. As the proper amino acids are brought into line one by one, peptide bonds
are formed between them, and a polypeptide chain result. Translation ends when one of the three
STOP codons in the mRNA is reached. The ribosome then comes apart into its two subunits, and the
mRNA and newly synthesized polypeptide chain are released. The ribosome, the mRNA, and the
tRNAs are then available to be used again,

RIBOSOME Where protein synthesis takes place

tRNA Serves as a link (or adaptor) between the messenger
RNA (mRNA) molecule and the growing chain of amino
acids that make up a protein
mRNA Contains the codon used for protein synthesis
CODON Three nucleotides that forms a unit of genomic
information encoding a particular amino acid or signaling
the termination of protein synthesis.
ANTICODON Trinucleotide sequence located at one end of tRNA
START CODON Trinucleotide that signals the start of the polypeptide
chain. AUG is the most common start codon and its
codes for Methionine
STOP CODON Trinucleotide that signals the termination of protein
synthesis. Stop codons are UAG, UAA, UGA

INHIBITORS OF PROTEIN SYNTHESIS

• Reversible inhibitors in Bacteria (Bacteriostatic Agents)
1. Tetracycline
2. Chloramphenicol
3. Erythromycin
4. Clindamycin
• Irreversible inhibitors in Bacteria (Bactericidal Agents)
1. Streptomycin

GENETIC CODE
• Set of rules which give a relationship between the nitrogenous bases and the amino acids in a
polypeptide chain.
• FEATURES:
• Most amino acids, assume > 1 codon; however, there is no one codon that specifies for >
1 amino acid.
• Coding ratio: 3 bases (letters) coding for 1 amino acid
MUTATION
• any chemical or physical change that alters the sequence of bases in the DNA molecule.
• Any alteration in the protein as a result of a change in all cell structure, because when the
genetic information in the DNA is altered, the message transcribed into RNA will also be
altered.
• MUTAGENS – substance that causes mutation either physical or chemical form.
TYPES OF MUTATION
SILENT MUTATION If abase substitution occurs in the third position of the codon there is
a good chance that a synonymous codon will be generated. Thus,
the amino acid sequence encoded by the gene is not changed and
the mutation is said to be silent.
“New codon specifies same amino acid”
MISSENSE MUTATION This type of mutation is a change in one DNA base pair that results
in the substitution of one amino acid for another in the protein made
by a gene.
“New codon specifies different amino acid”
NONSENSE MUTATION A nonsense mutation is also a change in one DNA base pair. Instead
of substituting one amino acid for another, however, the altered DNA
sequence prematurely signals the cell to stop building a protein. This
type of mutation results in a shortened protein that may function
improperly or not at all.
“New codon is a stop codon”
FRAMESHIFT MUTATION 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 code for one amino acid. A frameshift mutation
shifts the grouping of these bases and changes the code for amino
acids. The resulting protein is usually nonfunctional.
“Insertions, deletions, and duplications can all be frameshift
mutations.”

BASIC PRINCIPLES OF HEREDITY

Terminologies
• Alleles: Genes that may replace one another at the same locus. Responsible for alternate or
contrasting characters
• Homozygous: When both alleles carry the same defect
• Heterozygous: When one allele is normal, and the counterpart is defective.
• Phenotype: The observed character expressed by the gene
• Genotype: Represents the set pattern of genes present in the cell.
AUTOSOMAL DOMINANT INHERITANCE
• only one copy of a disease allele is necessary for an individual to be susceptible to expressing
the phenotype.
• Affected men and women transmit the abnormality to their children. When an affected
heterozygote parent (Dd) has a normal spouse (dd), half of the progeny will have the disease.
 • With each pregnancy, there is a one in two (50%) chance the offspring will inherit the disease
allele.
• Male-to-male transmission can be observed.
• Examples of diseases with autosomal dominant inheritance are chondrodystrophy (dwarfism)
and Huntington disease.
AUTOSOMAL RECESSIVE INHERITANCE
• Autosomal recessive inheritance, two copies of a disease allele are required for an individual
to be susceptible to expressing the phenotype.
• Typically, the parents of an affected individual are not affected but are gene carriers.
• When both father and mother are carriers, one-quarter of siblings express the disease (both
alleles abnormal), another one-quarter of siblings are normal, and half of the children are
carriers.
• As with autosomal dominant inheritance, the proportion of affected males should be equal to
the proportion of affected females in a given population.
• Examples of diseases with autosomal recessive inheritance include phenylketonuria, albinism,
galactosemia, sickle cell anemia and cystic fibrosis.
SEX-LINKED (X-LINKED) RECESSIVE INHERITANCE
• In the autosomal conditions, the disease occurs in both sexes with equal frequency. But in sex-
linked conditions, X-chromosome carries the abnormal gene.
• When a normal male carries a carrier female (unaffected parent), the children can be affected
male (25%), female carrier (25%), normal male (25%) and normal female (25%).
• All male children of an affected male and normal female will be normal; but all female children
will be carriers since they inherit the abnormal X from their father.
• There is no male-to-male transmission, but male-to female and female-to-male transmission of
the affected X can occur. X-linked traits are expressed in males who are hemizygous (XY) for
the condition, but not in-females who may be heterozygous (XX)
• Hemophilia, glucose-6-phosphate dehydrogenase deficiency, pseudohypertrophic muscular
dystrophy (Duchenne type), and red-green color blindness are examples of sex-linked
recessive inheritance.
FOUR CHROMOSOMAL ABNORMALITIES
1. TURNER SYNDROME
• Turner syndrome is a chromosomal condition that alters development in females.
Women with this condition tend to be shorter than average and are usually unable to
conceive a child (infertile) because of an absence of ovarian function.
• Other features of this condition that can vary among women who have Turner syndrome
include extra skin on the neck (webbed neck), puffiness or swelling (lymphedema) of
the hands and feet, skeletal abnormalities, heart defects and kidney problems.
2. KLINEFELTER SYNDROME
• Also known as the XXY condition, is a term
used to describe males who have an extra X
chromosome in most of their cells.
• Instead of having the usual XY chromosome
pattern that most males have, these men
have an XXY pattern.
• Even though all men with Klinefelter
syndrome have the extra X chromosome, not
every XXY male has all those symptoms.

3. DOWN SYNDROME / TRISOMY 21

• A genetic disorder and the most common autosomal chromosome abnormality in
humans, where extra genetic material from chromosome 21 is transferred to a newly
formed embryo.
• These extra genes and DNA cause changes in development of the embryo and fetus
resulting in physical and mental abnormalities.
• Each patient is unique and there can be
great variability in the severity of symptoms.
• In patients with Down syndrome, an error
occurs in the coming together of
chromosome 21.
• The extra genetic material is responsible for
the developmental abnormalities that occur.
• Instead of 46 chromosomes plus two sex
chromosomes, there are 47.

4. CRI DU CHAT OR CRY OF THE CAT

SYNDROME
• Cri du chat syndrome (CdCS or 5p-) is a rare genetic disorder in which a variable
portion of the short arm of chromosome 5 is missing or deleted (monosomic).
• Symptoms vary greatly from case to case depending upon the exact size and location of
the deleted genetic material.
• Common symptoms include a distinctive cry that resembles the mewing of a cat,
characteristic facial features, slow growth, and microcephaly, a condition that indicates
that head circumference is smaller than would be expected for an infant's age and sex.