Protein Synthesis and Cell Reproduction: by Edget Abebe

Protein synthesis
and Cell
Reproduction
By Edget Abebe
04/06/2021 cell reproduction Edget 1

Outlines
• DNA, Gene and RNA
• Gene expression and protein synthesis
• DNA replication
• Cell reproduction, the cell cycle
• Phases of Mitosis
• Regulation of the cell cycle
• Meiosis

Genetic control of protein synthesis and cell
reproduction
• The “central dogma of molecular biology” states that genetic
information flows unidirectionally from DNA to proteins
• Deoxyribonucleic acid (DNA) is an informational molecule that
contains in the sequence of its nucleotides the information required
to build all the proteins and RNA of an organism,

DNA is made from
1. Phosphoric Acid
2. Deoxyribose sugar
3. Nitrogenous bases:- purines :- Adenine and Guanine
pyrimidines:- Thymine and cytosine

• Gene:- a segment of DNA that • Gene expression:- the
codes for a specific protein translation of genetic
• Humans have 20,000-25,000 information into proteins
genes which account for 3% of • Steps of gene expression
DNA DNA →RNA → Protein

RNA
 RNA which stands for Ribose nucleic acid :- It is transcribed from

DNA.
Very similar to DNA except for

RNA is single stranded while DNA is double stranded
 RNA nucleotides contain ribose while DNA contains deoxyribose
 RNA has the base uracil rather than thymine that is present in
DNA.
 RNA is central to the synthesis of proteins
different types of RNA play different role in protein formation:

Types of RNA
1. Precursor messenger RNA (pre-mRNA)
is processed in the nucleus to form mature messenger RNA (mRNA)
• Has two segments Introns and exons
2. Small nuclear RNA (snRNA)
 directs the splicing of pre-mRNA to form mRNA
3. Messenger RNA(mRNA) : carries the genetic code to the

cytoplasm to control the type of protein formed
• Groups of 3 bases in mRNA, called “codons” code for each

individual amino acid in the protein made by that gene
Types of RNA cont.
4. Transfer RNA:
• transports activated amino acids to the ribosomes to assemble the

protein molecule.
5. Ribosomal RNA:
• forms ribosomes, the physical and chemical structures on which

protein molecules are actually assembled.
6. MicroRNAs (miRNAs):-
• regulate gene transcription and translation.

RNA processing (Transcription)
• processes whereby a section of DNA gets “read” and

chemically “photocopied” into a molecule of RNA
• RNA molecules are produced by copying part of DNA into a

complementary sequence of RNA
• This process is started and controlled by an enzyme called RNA

polymerase
04/06/2021 11
cell reproduction Edget
RNA polymerase
• binds with the Promoter region
DNA,
• unwinds the double helix and
breaks the bonds between the
nucleotides, making the DNA
single stranded.
• From one of the DNA strands,
RNA molecule is synthesized

Steps of transcription
Initiation:
• The DNA molecule unwinds and separates to form a small open
complex.
• RNA polymerase binds to the promoter of the template strand
(also known as the 'sense strand' or 'coding strand’).
• The synthesis of RNA proceeds in a 5' to 3' direction, so the
template strand must be 3' to 5
Elongation:
• RNA polymerase moves along the template strand, synthesizing
an mRNA molecule

Steps of transcription cont.
Termination
• Termination in eukaryotes is more complicated, involving the

addition of additional adenine nucleotides at the 3' of the
RNA transcript
Processing.
• After transcription the RNA molecule is processed in a

number of ways: introns are removed and the exons are
spliced together to form a mature mRNA
Translation
• is the synthesis of protein from RNA.
• During translation, the genetic code in the sequence of RNA

is “read” by transfer RNA (tRNA), and then amino acids
carried by the tRNA are covalently linked together to form a
polypeptide chain

Regulation of Gene Expression

Control of biochemical activity in the cell
• There are two mechanisms to control all cellular activities
1. genetic regulation:- in which the degree of activation of the genes

and the formation of gene products are themselves controlled
From transcription to protein synthesis
Differential regulation and differential function of cells
2. Enzyme regulation:- the activity levels of already formed enzymes

in the cell are controlled.

Control of biochemical activity in the cell
• Expression of genes requires
1. Promoters:- bases (TATAAA) called the TATA box, the binding
site for the TATA-binding protein and several other important
transcription factors
2. Enhancers: which are regions of DNA that can bind
transcription factors
3. Chromosomal insulators: separation of active genes that are
being transcribed from genes that are repressed
Histone: hold the DNA in a compacted state in a chromosome

making it unavailable for gene expression
Enzyme Activation. Enzymes that are normally inactive often can

be activated when needed.
Mechanism of Gene Regulation
Mechanisms of gene regulation include:
• Regulating the rate of transcription. This is the most economical

method of regulation.
• Regulating the processing of RNA molecules, including

alternative splicing to produce more than one protein product
from a single gene.
• Regulating the stability of mRNA molecules.
• Regulating the rate of translation.

DNA Replication
Occurs during interphase of cell cycle
1 DNA molecule untwisted
Each parent strand serves as template for

new strand
= 2 new DNA molecules,
each ½ old & ½ new
= semi-conservative replication

Enzymes break Hydrogen bonds between 2
strands
= unwinds & exposes nucleotide bases
Free nucleotides pair with exposed bases
Each parent strand has new one made on it

= twist together to form double helix

Enzymes of DNA replication
DNA helicase
unzips the double helix of DNA by breaking hydrogen bonds

between the base pairs
It forms “Y” shaped replication Fork thus the two separate
strands serve as templates to make new strand
DNA primase
Generates the RNA primer which serve as the starting point of

DNA replication
DNA replication cont.
DNA polymerase
Binds to primer of the” and walks along adding new nucleotides.
Adds nucleotides in the 5′ to 3′ direction
“leading strand” is oriented in the 3′ to 5′ direction, toward the

replication fork, while the “lagging strand” is oriented 5′ to 3′,
 DNA polymerase only adds nucleotides in the 5′ to 3′ direction
In the lagging strand fragments of DNA called Okazaki fragments

are made for DNA replication to progress in the 5′ to 3′ direction

DNA replication cont.
DNA ligase,
joins the Okazaki fragments to form a single unified strand
Exonuclease
removes the RNA primers from the original strands, and the primers are
replaced with appropriate bases.
 Another exonuclease “proofreads” the newly formed DNA, checking

and clipping off any mismatched or unpaired residues
Topoisomerase
can transiently break the phosphodiester bond in the backbone of the

DNA strand to prevent the DNA in front of the replication fork from
being overwound.
DNA and Chromosomes
DNA is packaged in to Chromosomes
• Chromosome is made from Histone and nonhistone proteins
Human cell 46 chromosomes
Types of chromosomes in human

Sex chromosomes
determine sex of organism Females XX ,Males XY
Autosomes
all other chromosomes in an organism
DNA and Chromosomes cont.
• When Chromosomes consist of two identical halves each half

is called a chromatid
• Chromatids form when DNA makes a copy of itself prior to

cell division
• When the cell divides each new cell receives one chromatid

The Cell Cycle
• Cell Cycle- events that make
up the life of a cell
2 Main Parts:
A. Interphase-cell growth and

DNA replication, the longest
takes 90% of the cell cycle
B. Mitosis- nuclear and

cytoplasmic division

Interphase
• most of cell’s time spent in
this part of cycle
A. G1- cell grows in size &
carries on metabolism
B. S- DNA is copied
C. G2- cell grows some
more and prepares to divide
• *Some cells enter G0 phase where

they remain and no longer grow or
divide (Ex: nerve cells)

G1 phase
• First phase within interphase
• It starts from the end of the previous M phase until the

beginning of DNA synthesis.
• It is also called the growth phase. During this phase the

biosynthetic activities of the cell occur.
• During G1 phase millions of proteins including all enzymes

required in S phase (for replication) are synthesized and the
cells prepare for replication.
S phase (synthetic phase)
• DNA is replicated, and a copy of each chromosome is made
• i.e., each chromosome has two sister chromatids.
• The amount of DNA in the cell is effectively doubled,
• DNA replication takes place simultaneous with chromosome

duplication
• It occupies about half of the cell-cycle time in a typical
mammalian cell

G2 phase
• During the gap between DNA synthesis and mitosis, the

cell will continue to grow.
• The G2 checkpoint control mechanism ensures that

everything is ready to enter the M (mitosis) phase and
divides.

M-phase(mitotic phase)
• cell divides in to two daughter cells with the same genetic
component as the parent cell.
• Chromosomes replicated during the S phase are divided
• Each daughter cell receives a copy of every chromosome.
• In actively dividing animal cells, the whole process takes about
one hour.
• During mitosis the new chromosomes are segregated between
the two daughter cells as the cells divide.

Mitosis
4 Stages of Mitosis
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase

1. Prophase
Chromosomes begin to condense,
 Spindle begins to form
Nuclear envelope begins to fall apart

2.Late Prophase/
prometaphase
 Nuclear envelope completely

falls apart
 Spindle fibres from each pole
attach to sister chromatids of
each chromosome
3. Metaphase
Chromosomes line up halfway between

spindle poles
4. Anaphase
• Sister chromatids of each chromosome

separate & move to opposite poles
(motor proteins attached to kinetochores
drag chromatids along microtubules)
• Spindle poles pushed apart by growing

microtubules

5.Telophase
1 of each type of chromosome reaches each
spindle pole
= 2 identical groups of chromosomes at each
cell pole
Chromosomes decondense
Nuclear envelope forms around each cluster

of chromosomes
= two nuclei, each with 2n # of
chromosomes

6. Cytokinesis

Cytokinesis in Animal Cells
Contractile ring mechanism
Halfway between cell’s poles,

plasma membrane constricts =
cleavage furrow
(ATP energy causes contraction of
actin filaments)
Cleavage furrow deepens until

cytoplasm split into 2
Cell cycle check points
Checkpoints
• cell cycle controlled by STOP & GO chemical signals at
critical points
• signals indicate if key cellular
processes have been
completed correctly

Cell cycle check point
3 major checkpoints:
G1/S (restriction check point)
• can DNA synthesis begin?
G2/M transition
• has DNA synthesis been completed correctly?
• commitment to mitosis
spindle checkpoint
• are all chromosomes attached to spindle?
• can sister chromatids separate correctly?

Cell cycle check points Cont.
G1/S (restriction check point)
• is most critical primary
decision point “restriction
point”
• if cell receives “GO”
signal, it divides
• 24
• external signals: “growth

factors”
• if cell does not receive
signal, it exits cycle &
switches to G0 phase
• non-dividing, working
state
Cell cycle control
G2/M transition,
• The control system triggers the early mitotic events that lead to
chromosome alignment on the mitotic spindle in metaphase.
metaphase-to-anaphase transition,
• The control system stimulates sister-chromatid separation,

leading to the completion of mitosis and cytokinesis

Cell cycle controls
• Cyclins
• regulatory proteins
• levels cycle in the cell
• Cdk’s
• cyclin-dependent kinases
• phosphorylates cellular proteins
• activates or inactivates proteins
• Cdk-cyclin complex
• triggers passage through different stages of cell cycle
• CKI- cyclin dependent kinase inhibitors
• Inhibit Cyclin and Cdk

Cell cycle control cyclins.
1. G1-cyclins,
• Helps govern the activities of the G1/S-cyclins
2. G1/S-cyclins :-
activate Cdks in late G1
trigger progression through Start, resulting in a commitment to
cell-cycle entry.
3. S-cyclins
 bind Cdks soon after progression through Start and help stimulate
chromosome duplication.
4. M-cyclins
activate Cdks that stimulate entry into mitosis at the G2/M
transition.
rising G1/S-cyclin levels lead to the formation of G1/S-Cdk complexes that
trigger progression through the Start transition.
S-Cdk complexes form at the start of S phase and trigger DNA replication, as
well as some early mitotic events.
M-Cdk are activated at the end of G2 and trigger entry into mitosis at the
G2/M transition.
A separate regulatory protein complex, the APC/C, initiates the metaphase-to
anaphase
04/06/2021
transition,. cell reproduction Edget 53
Regulation of cell division
• Frequency of cell division
Cell division & DNA replication
regulated so that: varies by cell type
Embryo
• cell cycle < 20 minute
DNA only replicated once before cell
division skin cells
• divide frequently throughout life
• 12-24 hours cycle
Cells that never divide do not
replicate DNA liver cells
• retain ability to divide, but keep it
in reserve
Cells don’t try to replicate DNA if • divide once every year or two
lack the energy & raw materials to mature nerve cells & muscle
complete process
cells
• do not divide at all after maturity
• permanently in G0
Extracellular signals for cell division and growth
1. Mitogens,
stimulate cell division, primarily by triggering a wave of G1/S-
Cdk
platelet-derived growth factor (PDGF)
epidermal growth factor (EGF ), erythropoietin,
2. Growth factors,
stimulate cell growth (an increase in cell mass) by promoting
the synthesis of proteins and other macromolecules and by
inhibiting their degradation.
3. Survival factors,
promote cell survival by suppressing apoptosis

CONTROL OF CELL DIVISION AND
CELL GROWTH
Turn off signals
• DNA damage during cell division blocks cell division
• Activation of regulatory genes causes deactivation of cdk

complexes thereby inhibiting cell division
• One of the regulatory gene activated is the p53,
• Its activation arrests the cell cycle

Cancer
Growth factors can create cancers
• Proto-oncogenes
• normal growth factor genes that become oncogenes
(cancer-causing) when mutated
• stimulates cell growth
• if switched “ON” can cause cancer
• Tumor-suppressor genes
• inhibits cell division
• if switched “OFF” can cause cancer
• example: p53
Cancer and cell growth
• Cancer is essentially a failure of cell division control
• unrestrained, uncontrolled cell growth
• lose checkpoint stops
• p53 protein halts cell division if it detects
damaged DNA
•
stimulates repair enzymes to fix DNA
•
forces cell into G0 resting stage
•
keeps cell in G1 arrest
•
causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity

Characteristics of Cancer cells
• unlimited growth : turn on growth promoter genes
• ignore checkpoints : turn off tumor suppressor genes (p53)
• escape apoptosis, immortality = unlimited divisions
• promotes blood vessel growth
• overcome anchor & density dependence: turn off touch-sensor gene

Two Types of Cell Division
Mitosis: Meiosis:
• Produces 2 genetically • Produces 4 genetically
identical cells different cells
• Happens throughout body • Cells only have ½ of genetic
info
Growth, cell replacement, • Happens only in gonads
tissue repair
Results in 4 genetically
 Also used for asexual different cells with ½ genetic
reproduction info of parent cell
= organisms clone selves
= sexual reproduction

Meiosis
• The form of cell division by which gametes, with half the
number of chromosomes, are produced.
• Meiosis is sexual reproduction. Diploid (2n)  haploid

(n)
• Two divisions (meiosis I and meiosis II).
• Sex cells divide to produce gametes (sperm or egg).

• Occurs only in gonads (testes or ovaries).
Male: spermatogenesis
Female: oogenesis
Stages in Meiosis I
• Meiosis I : four phases:
a. prophase I
b. metaphase I
c. anaphase I
d. telophase I

Prophase I
• Longest and most complex phase (90%).
• Chromosomes condense.
• Synapsis occurs: homologous chromosomes come together
to form a tetrad.
• Tetrad is two chromosomes or four chromatids (sister and
non sister chromatids).
• Crossing over :- homologous chromosomes exchange
genetic materials

Prophase I

Prophase I

Homologous Chromosomes
• Pair of chromosomes (maternal and paternal) that are similar in shape
and size.
• Homologous pairs (tetrads) carry genes controlling the same
inherited traits.
• Each locus (position of a gene) is in the same position on
homologues.
• Humans have 23 pairs of homologous chromosomes.
a. 22 pairs of autosomes
b. 01 pair of sex chromosomes

Metaphase I
• Shortest phase
• Tetrads align on the metaphase plate.
• INDEPENDENT ASSORTMENT OCCURS:

1. Orientation of homologous pair to poles is random.
2. Variation

Anaphase I
• Spindle fibers attach to the centromeres of each pair.
• Homologous chromosomes separate and move to opposite ends
of the cell.
• Centromeres DO NOT split like they do in mitosis
• Now each cell will get one chromosome from each homologous
pair.

Telophase I
• Each pole now has haploid set of chromosomes.
• Cytokinesis occurs and two haploid daughter cells are formed

MEIOSIS II
• Is basically just like mitosis, but remember the chromosomes do not
duplicate in interphase II.
Prophase II
• Chromosomes begin to line up in the middle of the cell.
• Spindle fibers begin to form
Metaphase II
• Chromosomes line up on the metaphase plate

Meiosis II cont.
Anaphase II
• Centromeres split
• Sister chromatids separate and move to opposite sides of the
cell
Telophase II
• Nuclei reform
• Spindle fibers disappear
• Cytoplasm divides into two.
• The number of chromosomes in each daughter cell has now been
reduced by half.

Thankyou

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Protein synthesis

04/06/2021 cell reproduction Edget 1

• DNA, Gene and RNA

• Gene expression and protein synthesis

• Cell reproduction, the cell cycle

• Regulation of the cell cycle

04/06/2021 cell reproduction Edget 2

• The “central dogma of molecular biology” states that genetic

information flows unidirectionally from DNA to proteins

• Deoxyribonucleic acid (DNA) is an informational molecule that

contains in the sequence of its nucleotides the information required

to build all the proteins and RNA of an organism,

04/06/2021 cell reproduction Edget 3

04/06/2021 cell reproduction Edget 4

04/06/2021 cell reproduction Edget 5

 RNA which stands for Ribose nucleic acid :- It is transcribed from

Very similar to DNA except for

 RNA is central to the synthesis of proteins

different types of RNA play different role in protein formation:

is processed in the nucleus to form mature messenger RNA (mRNA)

• Has two segments Introns and exons

2. Small nuclear RNA (snRNA)

 directs the splicing of pre-mRNA to form mRNA

3. Messenger RNA(mRNA) : carries the genetic code to the

• Groups of 3 bases in mRNA, called “codons” code for each

• transports activated amino acids to the ribosomes to assemble the

• forms ribosomes, the physical and chemical structures on which

• regulate gene transcription and translation.

• processes whereby a section of DNA gets “read” and

• RNA molecules are produced by copying part of DNA into a

• This process is started and controlled by an enzyme called RNA

04/06/2021 cell reproduction Edget 12

04/06/2021 cell reproduction Edget 13

• Termination in eukaryotes is more complicated, involving the

• After transcription the RNA molecule is processed in a

• During translation, the genetic code in the sequence of RNA

04/06/2021 cell reproduction Edget 15

04/06/2021 cell reproduction Edget 18

1. genetic regulation:- in which the degree of activation of the genes

From transcription to protein synthesis

Differential regulation and differential function of cells

2. Enzyme regulation:- the activity levels of already formed enzymes

04/06/2021 cell reproduction Edget 19

Histone: hold the DNA in a compacted state in a chromosome

Enzyme Activation. Enzymes that are normally inactive often can

Mechanisms of gene regulation include:

• Regulating the rate of transcription. This is the most economical

• Regulating the processing of RNA molecules, including

• Regulating the stability of mRNA molecules.

• Regulating the rate of translation.

Occurs during interphase of cell cycle

1 DNA molecule untwisted

Each parent strand serves as template for

04/06/2021 cell reproduction Edget 23

Free nucleotides pair with exposed bases

Each parent strand has new one made on it

04/06/2021 cell reproduction Edget 24

unzips the double helix of DNA by breaking hydrogen bonds

Generates the RNA primer which serve as the starting point of

Binds to primer of the” and walks along adding new nucleotides.

Adds nucleotides in the 5′ to 3′ direction

“leading strand” is oriented in the 3′ to 5′ direction, toward the