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GENETIC CONTROL OF PROTEIN
SYNTHESIS, CELL FUNCTION AND
CELL REPRODUCTION
CELL PHYSIOLOGY
LEARNING OBJECTIVES
At the end of the session, students should be able to:
1. determine the basic structure of DNA and RNA and its
relation to protein synthesis,
2. understand the cellular and molecular mechanism of gene
expression, cell reproduction and aging.
GENERAL OVERVIEW OF THE
CENTRAL DOGMA OF GENE
EXPRESSION
Gene: section of DNA that creates a
specific protein
Approx 30,000 human genes
Proteins are used to build cells and
tissue
Gene expression involves two
processes:
1) Transcription
2) Translation
STRUCTURE OF DNA
• Discovered in 1953 by two
scientists:
• James Watson (USA)
• Francis Crick (GBR)
• Known as the double-helix
model.
double-helix structure
H
H
H
O
CH2
Base
DNA nucleotide
Phosphate
Deoxyribose
H
H
OH
O
CH2
Base
Phosphate
Ribose
5′
OH OH
4′ 1′
3′ 2′
5′
4′ 1′
3′ 2′
O
O
O
P
O–
O
O
P
O–
O
H
H H
H
NUCLEOTIDES OF DNA AND
RNA
RNA nucleotide
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Complementary base pairs in DNA
NH2
N O
N
O
N O
N
Adenine (A)
Guanine (G)
Thymine (T)
Bases
Backbone
Cytosine (C)
O
H
H
H
H
H
H
O
O
O
O–
P CH2
O–
H
H
H
H
H
H
H
O
O
O
O
P CH2
O–
NH2
N
N
H
N
N
H
H
H
H
H
O
O
O
O
P CH2
O–
NH2
H
N
N
N
H
N
H
H
H
OH
H
H
O
O
O
O
P CH2
O–
Single
nucleotide
Phosphodiester
linkage
Sugar (deoxyribose)
Phosphate
3′
5′
5′
4′ 1′
2′
3′
5′
4′ 1′
2′
3′
5′
4′ 1′
2′
3′
5′
4′ 1′
2′
3′
CH3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
H
N H
N
N
N
G
NH2
H
P
S
P
S
P
5′ end
3′ end
H NH2
N
N
H
H
H
H
H
O
O
O
O
P CH2
O–
H
H
H
OH
H
H
O
O
O
O
P CH2
O–
H
H
H
H
H
O
O
O
O
P CH2
O–
CH2
H
H
H
H
H
O
O
O
O–
P
O–
T
2 nm
2 hydrogen bonds
between T and A
T
A
G C
T A
P
P
P
P
P
S
S
S
S
S
S
S
S
S
A
C
G
C G
C G
G C
G C
G
C
G C
C
P
P
S
P
P
P
P
P
S
S
S
S
S
P
P
P
P
P
P
P
P
P
P
S
S S
S
S
S
S
S
S
P
S
S
P
P
P
S
S
S
S
P
3′
5′
G
S
3′
5′
S
A
P
P
C
T A
O
N
N
N
N
A
H
H NH2
N
O
H CH3
H
T
H
H
H2N
N
N C
O
3′ end
5′ end
H
H
H
H
O
O
O
O–
P
CH2
O
H
H
H
H
H
H
O
O
O
O–
P
CH2
O
H
H
H
H
O
O
O
O–
P
CH2
O–
H
H
H
H
O
O
O
O–
P
CH2
O
HO
N
O
H
CH3
H
T
O
N
H N
N
N
G
H2N
H
H
H
N
N
N
N A
H
H2N H
3 hydrogen bonds
between T and A
Transcription takes place in the nucleus
 1) DNA double helix is broken apart
 2) mRNA nucleotides match up
 3) Finished mRNA detaches, and moves to a ribosome
•Transcription is the process by which a molecule of
DNA is copied into a complementary strand of
RNA.
•This is called messenger RNA (mRNA) because it
acts as a messenger between DNA and the
ribosome where protein synthesis is carried out.
TYPES OF RNA
MOLECULES
© John Wiley & Sons, Inc.
 Messenger RNAs (mRNAs)—intermediates that carry genetic information
from DNA to the ribosomes.
 Transfer RNAs (tRNAs)—adaptors between amino acids and the codons in
mRNA.
 Ribosomal RNAs (rRNAs)—structural and catalytic components of
ribosomes.
TYPES OF RNA
MOLECULES
 Small nuclear RNAs (snRNAs)—structural components of spliceosomes.
 Micro RNAs (miRNAs)—short single-stranded RNAs (20 to 22 bp) that block
expression of complementary mRNAs.
 RNAi is similar to miRNA (RNA interference, double strand RNA, plant) siRNA
(small interference)
 piRNA (Piwi-interacting RNA) is a small non-coding RNA molecules
© John Wiley & Sons, Inc.
• RNA polymerization is similar to DNA synthesis
EXCEPT:
1. The precursors are NTPs (not dNTPs).
2. No primer is needed to initiate synthesis.
3. Uracil is inserted instead of thymine.
The Transcription Process: RNA Synthesis
Chemical reaction involved in the RNA polymerase catalyzed synthesis of RNA
on a DNA template strand
The Transcription Process
• Transcription is divided
into three steps for both
prokaryotes and eukaryotes.
They are:
1. Initiation
2. Elongation
3. Termination.
THE TRANSCRIPTION BUBBLE
© John Wiley & Sons, Inc.
Eukaryotes:
--several RNA polymerases
--no direct recognition binding
--transcriptional factors
TRANSCRIPTION AND TRANSLATION IN
EUKARYOTES
© John Wiley & Sons, Inc.
THE TRANSCRIPTION BUBBLE
© John Wiley & Sons, Inc.
Prokaryotes:
--RNA polymerase binds specific
nucleotide sequences (promoter
regions) plus transcriptional
factors
--Single RNA polymerase
--DNA unwinding (AT regions)
TRANSCRIPTION AND TRANSLATION IN
PROKARYOTES
© John Wiley & Sons, Inc.
ELONGATION
© John Wiley & Sons, Inc.
Rho-independent terminators—do not require 
intrinsic termination)
EUKARYOTIC TRANSCRIPTION:
RNA POLYMERASES
A. RNA POLYMERASE I
LOCATED IN THE NUCLEOLUS, TRANSCRIBES THE 3 MAJOR
RIBOSOMAL RNA
B. RNA POLYMERASE II
LOCATED IN THE NUCLEOPLASM, TRANSCRIBE MESSENGER RNA
AND SOME SMALL NUCLEAR RNA
C. RNA POLYMERASE III
LOCATED IN THE NUCLEOPLASM, TRANSCRIBE TRANSFER RNA
AND SOME SMALL NUCLEAR RNA
GENERAL
TRANSCRIPTIONAL FACTOR
(GTF)
Also known as basal transcriptional factors, are a class
of protein transcription factors that bind to specific sites (promoter)
on DNA to activate transcription of genetic information from DNA
to messenger RNA.
 TFIIA
 TFIIB
 TFIID
 TFIIE
 TFIIF
 TFIIH
The eukaryotic basal
transcription complex
TFIID complex
TFIID
TATA-binding protein
TBP-associated protein
RNA CHAIN
ELONGATION
© John Wiley & Sons, Inc.
THE 3’
POLY(A) TAIL
© John Wiley & Sons, Inc.
RNA Chain termination
MODIFICATIONS TO EUKARYOTIC
PRE-MRNAS
REMOVAL OF INTRON
SEQUENCES BY RNA
SPLICING
© John Wiley & Sons, Inc.
 Codon: Combination of 3
mRNA nucleotides
 Each mRNA codon matches
with 1 of 20 amino acids
 Ribosome reads codons 1 at a
time
 Codon AUG = Methionine
(Start)
 Codon GUU = Valine
 Codons UAA or UAG or UGA
= Stop
H
P
O
O
HO
O
O
CH2
NH2
N
NH
N
N
H
OH
P
O
O
HO
O
O
CH2
NH2
N
N
N
N
H
P
O
OH
HO
O
O
CH2
NH2
N
N
N
N
O
Guanine
Adenine
Adenine
Arginine
 Defined: process of decoding a mRNA molecule into a polypeptide
chain or protein.
 Step 1: mRNA enters ribosome
 Step 2: Ribosome reads one mRNA codon at a time
 Step 3: tRNA delivers amino acids until a protein is created
Transfer
RNA
(tRNA)
(a) Ribbon model
3′ end
(acceptor
site)
5′ end
Double helix
Double helix
Anticodon
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Anticodon loop
3’ end carries
amino acid
Because the codon and anticodon don’t match, the
wrong amino acid will not be delivered.
This is why the
anticodon is
important!
Now the codon and
anticodon match. This
ensures the proper
amino acid (serine) is
delivered.
ANYTHING
ACID
AMINE
Protein Synthesis
C
O
OH
C
N
H
H
H
C
HO H
C
H
O
C
N
H
H
H
C
H H
C
H
O
OH
C
N
H
H
H
C
HO H
Serine
C
H
O
OH
C
N
H
H
H
C
H H
Alanine
H
C
O
OH
C
R
N
H
H
Amino Acid
H2O
GAU AUG CCG AGU CCA GGA UCU UGA
tRNA
UAC
tRNA
GGC
tRNA
UCA
tRNA
GGU
tRNA
CCU
tRNA
AGA
Meth
ionin
e
Pro
-
line
Serin
e
Pro-
line
Gly-
cine
Serin
e
Ribosome
Questions to answer:
1) List the amino acids that
will be delivered to this
ribosome.
2) What is the anticodon of each
codon?
3) When finished, how many
amino acids in size is this
protein?
 Interphase
 G1 - primary growth
 S - genome replicated
 G2 - secondary growth
 M - mitosis
 C - cytokinesis
CHROMOS
OMES
 All eukaryotic cells store genetic information
in chromosomes.
 Most eukaryotes have between 10 and 50
chromosomes in their body cells.
 Human cells have 46 chromosomes.
 23 nearly-identical pairs
SALIENT FEATURES OF
DNA REPLICATION
1. Both strand of DNA in each chromosome are replicated.
2. Both entire strand of the DNA helix are replicated from end to end.
3. The primary enzymes for replicating DNA are complex enzymes called DNA
polymerase. RNA primer is needed for elongation.
4. Formation of each new DNA strand occurs simultaneously in hundreds of
segments along each of the tow strands
0.5 µm
Chromosome
duplication
(including DNA
synthesis)
Centromere
Separation
of sister
chromatids
Sister
chromatids
Centrometers
Sister chromatids
MITOSIS
•
• (1)Prophase
• (2)Metaphase
• (3)Anaphase
• (4)Telophase
•PMAT
Interphase 1 2
3
4
Cytokinesis
Prophase
• The chromatin fibers become
more tightly coiled, condensing
into discrete chromosomes
• The nucleoli disappear.
• The mitotic spindle begins to form.
• The centrosomes move away from
each other, apparently propelled
by the lengthening microtubules
between them.
PROPHASE
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
Metaphase
•The chromosomes’ centromeres lie on
the metaphase plate.
• For each chromosome, the
kinetochores of the sister
chromatids are attached to
kinetochore microtubules coming
from opposite poles.
METAPHASE
Spindle
Metaphase
plate
Centrosome at
one spindle pole
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Metaphase chromosome
Kinetochore
Kinetochore
microtubules
Centromere
region of
chromosome
Sister Chromatids
Microtubules Chromosomes
Sister
chromatids
Aster
Centrosome
Metaphase
plate
Kineto-
chores
Kinetochore
microtubules
0.5 µm
Overlapping
nonkinetochore
microtubules
1 µm
Centrosome
Anaphase
•Anaphase begins when the two sister
chromatids of each pair suddenly part.
• The cell elongates as the
nonkinetochore microtubules
lengthen.
• By the end of anaphase, the two ends
of
the cell have equivalent—and
complete—collections of chromosomes.
ANAPHASE
Daughter
chromosomes
Telophase
•Nuclear envelopes arise from
the fragments of the parent
cell’s nuclear envelope and
other portions of the
endomembrane system.
• The chromosomes become
less condensed.
• Mitosis, the division of one
nucleus into two genetically
identical nuclei, is now
complete.
TELOPHASE AND CYTOKINESIS
Nucleolus
forming
Cleavage
furrow
Nuclear
envelope
forming
Daughter cells
Cleavage furrow
Contractile ring of
microfilaments
Daughter cells
100 µm
1 µm
Vesicles
forming
cell plate
Wall of
patent cell Cell plate New cell wall
(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM)
Cdk / G1
cyclin
Cdk / G2
cyclin (MPF)
G2
S
G1
C
M
G2 / M checkpoint
G1 / S checkpoint
APC
Active
Inactive
Active
Inactive
Inactive
Active
mitosis
cytokinesis
MPF = Mitosis
Promoting Factor
APC = Anaphase
Promoting Complex
• Replication completed
• DNA integrity
Chromosomes attached
at metaphase plate
Spindle checkpoint
• Growth factors
• Nutritional state of cell
• Size of cell
MOLECULAR BASIS OF CELL AGING
Proliferative
capacity
Number of cell divisions
Finite
Replicative
Life Span
"Mortal"
Infinite
Replicative
Life Span
"Immortal"
EXCEPTIONS
Germ line
Early embryonic cells (stem cells)
Many tumor cells
The main factors acting in cell aging process
AGING
Mitochondria
Free radical
by-product
intercellular oxidative stress
(increase senescence)
CELL CYCLE
REGULATION
PROTEIN REGULATOR
MUTATION(CANCER
SUPRESSOR,
CYCLINS, MAP
KINASE)
Cell malignancy
or cell death
Telomeres are…
 Repetitive DNA sequences at
the ends of all human
chromosomes
 They contain thousands of
repeats of the six-nucleotide
sequence, TTAGGG
 In humans there are 46
chromosomes and thus 92
telomeres (one at each end)
CHROMOSOME
TTAGGGTTAGGGTTAGGGTTAGGGTTAGGG
AATCCCAATCCC
5’
3’
TELOMERE
GENETIC CONTROL OF PROTEIN SYNTHESIS AND CELL FUNCTION

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GENETIC CONTROL OF PROTEIN SYNTHESIS AND CELL FUNCTION

  • 1. GENETIC CONTROL OF PROTEIN SYNTHESIS, CELL FUNCTION AND CELL REPRODUCTION CELL PHYSIOLOGY
  • 2. LEARNING OBJECTIVES At the end of the session, students should be able to: 1. determine the basic structure of DNA and RNA and its relation to protein synthesis, 2. understand the cellular and molecular mechanism of gene expression, cell reproduction and aging.
  • 3. GENERAL OVERVIEW OF THE CENTRAL DOGMA OF GENE EXPRESSION
  • 4.
  • 5.
  • 6.
  • 7. Gene: section of DNA that creates a specific protein Approx 30,000 human genes Proteins are used to build cells and tissue Gene expression involves two processes: 1) Transcription 2) Translation
  • 8. STRUCTURE OF DNA • Discovered in 1953 by two scientists: • James Watson (USA) • Francis Crick (GBR) • Known as the double-helix model.
  • 10. H H H O CH2 Base DNA nucleotide Phosphate Deoxyribose H H OH O CH2 Base Phosphate Ribose 5′ OH OH 4′ 1′ 3′ 2′ 5′ 4′ 1′ 3′ 2′ O O O P O– O O P O– O H H H H NUCLEOTIDES OF DNA AND RNA RNA nucleotide
  • 11.
  • 12. Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings. Complementary base pairs in DNA
  • 13. NH2 N O N O N O N Adenine (A) Guanine (G) Thymine (T) Bases Backbone Cytosine (C) O H H H H H H O O O O– P CH2 O– H H H H H H H O O O O P CH2 O– NH2 N N H N N H H H H H O O O O P CH2 O– NH2 H N N N H N H H H OH H H O O O O P CH2 O– Single nucleotide Phosphodiester linkage Sugar (deoxyribose) Phosphate 3′ 5′ 5′ 4′ 1′ 2′ 3′ 5′ 4′ 1′ 2′ 3′ 5′ 4′ 1′ 2′ 3′ 5′ 4′ 1′ 2′ 3′ CH3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
  • 14. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display H N H N N N G NH2 H P S P S P 5′ end 3′ end H NH2 N N H H H H H O O O O P CH2 O– H H H OH H H O O O O P CH2 O– H H H H H O O O O P CH2 O– CH2 H H H H H O O O O– P O– T 2 nm 2 hydrogen bonds between T and A T A G C T A P P P P P S S S S S S S S S A C G C G C G G C G C G C G C C P P S P P P P P S S S S S P P P P P P P P P P S S S S S S S S S P S S P P P S S S S P 3′ 5′ G S 3′ 5′ S A P P C T A O N N N N A H H NH2 N O H CH3 H T H H H2N N N C O 3′ end 5′ end H H H H O O O O– P CH2 O H H H H H H O O O O– P CH2 O H H H H O O O O– P CH2 O– H H H H O O O O– P CH2 O HO N O H CH3 H T O N H N N N G H2N H H H N N N N A H H2N H 3 hydrogen bonds between T and A
  • 15. Transcription takes place in the nucleus  1) DNA double helix is broken apart  2) mRNA nucleotides match up  3) Finished mRNA detaches, and moves to a ribosome
  • 16. •Transcription is the process by which a molecule of DNA is copied into a complementary strand of RNA. •This is called messenger RNA (mRNA) because it acts as a messenger between DNA and the ribosome where protein synthesis is carried out.
  • 17.
  • 18. TYPES OF RNA MOLECULES © John Wiley & Sons, Inc.  Messenger RNAs (mRNAs)—intermediates that carry genetic information from DNA to the ribosomes.  Transfer RNAs (tRNAs)—adaptors between amino acids and the codons in mRNA.  Ribosomal RNAs (rRNAs)—structural and catalytic components of ribosomes.
  • 19. TYPES OF RNA MOLECULES  Small nuclear RNAs (snRNAs)—structural components of spliceosomes.  Micro RNAs (miRNAs)—short single-stranded RNAs (20 to 22 bp) that block expression of complementary mRNAs.  RNAi is similar to miRNA (RNA interference, double strand RNA, plant) siRNA (small interference)  piRNA (Piwi-interacting RNA) is a small non-coding RNA molecules © John Wiley & Sons, Inc.
  • 20. • RNA polymerization is similar to DNA synthesis EXCEPT: 1. The precursors are NTPs (not dNTPs). 2. No primer is needed to initiate synthesis. 3. Uracil is inserted instead of thymine. The Transcription Process: RNA Synthesis
  • 21. Chemical reaction involved in the RNA polymerase catalyzed synthesis of RNA on a DNA template strand
  • 22. The Transcription Process • Transcription is divided into three steps for both prokaryotes and eukaryotes. They are: 1. Initiation 2. Elongation 3. Termination.
  • 23.
  • 24.
  • 25. THE TRANSCRIPTION BUBBLE © John Wiley & Sons, Inc. Eukaryotes: --several RNA polymerases --no direct recognition binding --transcriptional factors
  • 26. TRANSCRIPTION AND TRANSLATION IN EUKARYOTES © John Wiley & Sons, Inc.
  • 27. THE TRANSCRIPTION BUBBLE © John Wiley & Sons, Inc. Prokaryotes: --RNA polymerase binds specific nucleotide sequences (promoter regions) plus transcriptional factors --Single RNA polymerase --DNA unwinding (AT regions)
  • 28. TRANSCRIPTION AND TRANSLATION IN PROKARYOTES © John Wiley & Sons, Inc.
  • 29.
  • 31. © John Wiley & Sons, Inc. Rho-independent terminators—do not require  intrinsic termination)
  • 32. EUKARYOTIC TRANSCRIPTION: RNA POLYMERASES A. RNA POLYMERASE I LOCATED IN THE NUCLEOLUS, TRANSCRIBES THE 3 MAJOR RIBOSOMAL RNA B. RNA POLYMERASE II LOCATED IN THE NUCLEOPLASM, TRANSCRIBE MESSENGER RNA AND SOME SMALL NUCLEAR RNA C. RNA POLYMERASE III LOCATED IN THE NUCLEOPLASM, TRANSCRIBE TRANSFER RNA AND SOME SMALL NUCLEAR RNA
  • 33. GENERAL TRANSCRIPTIONAL FACTOR (GTF) Also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA.  TFIIA  TFIIB  TFIID  TFIIE  TFIIF  TFIIH
  • 36. RNA CHAIN ELONGATION © John Wiley & Sons, Inc.
  • 37. THE 3’ POLY(A) TAIL © John Wiley & Sons, Inc. RNA Chain termination
  • 39. REMOVAL OF INTRON SEQUENCES BY RNA SPLICING © John Wiley & Sons, Inc.
  • 40.  Codon: Combination of 3 mRNA nucleotides  Each mRNA codon matches with 1 of 20 amino acids  Ribosome reads codons 1 at a time  Codon AUG = Methionine (Start)  Codon GUU = Valine  Codons UAA or UAG or UGA = Stop
  • 42.  Defined: process of decoding a mRNA molecule into a polypeptide chain or protein.  Step 1: mRNA enters ribosome  Step 2: Ribosome reads one mRNA codon at a time  Step 3: tRNA delivers amino acids until a protein is created
  • 44. (a) Ribbon model 3′ end (acceptor site) 5′ end Double helix Double helix Anticodon Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Anticodon loop 3’ end carries amino acid
  • 45. Because the codon and anticodon don’t match, the wrong amino acid will not be delivered. This is why the anticodon is important! Now the codon and anticodon match. This ensures the proper amino acid (serine) is delivered.
  • 46. ANYTHING ACID AMINE Protein Synthesis C O OH C N H H H C HO H C H O C N H H H C H H C H O OH C N H H H C HO H Serine C H O OH C N H H H C H H Alanine H C O OH C R N H H Amino Acid H2O
  • 47. GAU AUG CCG AGU CCA GGA UCU UGA tRNA UAC tRNA GGC tRNA UCA tRNA GGU tRNA CCU tRNA AGA Meth ionin e Pro - line Serin e Pro- line Gly- cine Serin e Ribosome Questions to answer: 1) List the amino acids that will be delivered to this ribosome. 2) What is the anticodon of each codon? 3) When finished, how many amino acids in size is this protein?
  • 48.
  • 49.
  • 50.  Interphase  G1 - primary growth  S - genome replicated  G2 - secondary growth  M - mitosis  C - cytokinesis
  • 51. CHROMOS OMES  All eukaryotic cells store genetic information in chromosomes.  Most eukaryotes have between 10 and 50 chromosomes in their body cells.  Human cells have 46 chromosomes.  23 nearly-identical pairs
  • 52.
  • 53. SALIENT FEATURES OF DNA REPLICATION 1. Both strand of DNA in each chromosome are replicated. 2. Both entire strand of the DNA helix are replicated from end to end. 3. The primary enzymes for replicating DNA are complex enzymes called DNA polymerase. RNA primer is needed for elongation. 4. Formation of each new DNA strand occurs simultaneously in hundreds of segments along each of the tow strands
  • 54.
  • 55. 0.5 µm Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Sister chromatids Centrometers Sister chromatids
  • 56.
  • 58. • (1)Prophase • (2)Metaphase • (3)Anaphase • (4)Telophase •PMAT Interphase 1 2 3 4 Cytokinesis
  • 59. Prophase • The chromatin fibers become more tightly coiled, condensing into discrete chromosomes • The nucleoli disappear. • The mitotic spindle begins to form. • The centrosomes move away from each other, apparently propelled by the lengthening microtubules between them. PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids
  • 60. Metaphase •The chromosomes’ centromeres lie on the metaphase plate. • For each chromosome, the kinetochores of the sister chromatids are attached to kinetochore microtubules coming from opposite poles. METAPHASE Spindle Metaphase plate Centrosome at one spindle pole
  • 61. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metaphase chromosome Kinetochore Kinetochore microtubules Centromere region of chromosome Sister Chromatids
  • 63. Anaphase •Anaphase begins when the two sister chromatids of each pair suddenly part. • The cell elongates as the nonkinetochore microtubules lengthen. • By the end of anaphase, the two ends of the cell have equivalent—and complete—collections of chromosomes. ANAPHASE Daughter chromosomes
  • 64. Telophase •Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and other portions of the endomembrane system. • The chromosomes become less condensed. • Mitosis, the division of one nucleus into two genetically identical nuclei, is now complete. TELOPHASE AND CYTOKINESIS Nucleolus forming Cleavage furrow Nuclear envelope forming
  • 65. Daughter cells Cleavage furrow Contractile ring of microfilaments Daughter cells 100 µm 1 µm Vesicles forming cell plate Wall of patent cell Cell plate New cell wall (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (SEM)
  • 66. Cdk / G1 cyclin Cdk / G2 cyclin (MPF) G2 S G1 C M G2 / M checkpoint G1 / S checkpoint APC Active Inactive Active Inactive Inactive Active mitosis cytokinesis MPF = Mitosis Promoting Factor APC = Anaphase Promoting Complex • Replication completed • DNA integrity Chromosomes attached at metaphase plate Spindle checkpoint • Growth factors • Nutritional state of cell • Size of cell
  • 67. MOLECULAR BASIS OF CELL AGING
  • 68.
  • 69. Proliferative capacity Number of cell divisions Finite Replicative Life Span "Mortal" Infinite Replicative Life Span "Immortal" EXCEPTIONS Germ line Early embryonic cells (stem cells) Many tumor cells
  • 70. The main factors acting in cell aging process AGING
  • 73. Telomeres are…  Repetitive DNA sequences at the ends of all human chromosomes  They contain thousands of repeats of the six-nucleotide sequence, TTAGGG  In humans there are 46 chromosomes and thus 92 telomeres (one at each end) CHROMOSOME TTAGGGTTAGGGTTAGGGTTAGGGTTAGGG AATCCCAATCCC 5’ 3’ TELOMERE

Editor's Notes

  1. General schema by which genes control cell function.
  2. Genes are located in the nuclei of all cells of the body, controls heredity from parents to children. It also control cell function by determining which substances are synthesized within cell-which structures, which enzymes, which chemicals.
  3. A twisted ladder with two long chains of alternating phosphates and sugars. The nitrogenous bases act as the “rungs” joining the two strands.
  4. Complementary base pairs in DNA 1.) Pyrimidine always pairs with purine 2.) The higher number of hydrogen bonds in GC pairings confer sequence-specific annealing properties
  5. Process by which the genetic information is conveyed from a double stranded DNA molecule to a single stranded RNA molecule. Only one strand of DNA serves as a template: – this is the transcribed or anti-sense strand.
  6. Salient Features of Transcription • RNA polymerase: – catalyzes the addition of one ribonucleotide at a time, – extending the RNA strand being synthesized in the 5’ to 3’ direction. • Promoter: – DNA sequences near the beginning of a gene. – These signal the RNA polymerase to begin transcription. • Terminators: – sequences within the RNA products, – which signal the RNA polymerase to stop transcription.
  7. A prokaryotic gene is a DNA sequence in the chromosome. The gene has three regions, each with a function in transcription : 1. A promoter sequence that attracts RNA polymerase to begin transcription at a site specified by the promoter. 2. The transcribed sequence, called the RNA-coding sequence. The sequence of this DNA corresponds with the RNA sequence of the transcript. 3. A terminator region that specifies where transcription will stop.
  8. A transcription unit is defined as that region of DNA that includes the signals for transcription initiation, elongation, and termination. The RNA product, which is synthesized in the 5'–3' direction, is the primary transcript. The common E. coli promoter that is used for most transcription has these consensus sequences: – For the -35 region the consensus is • 5’-TTGACA-3’. – For the -10 region (previously known as a Pribnow box), the consensus is • 5’-TATAAT-3’. These regions are located 35 and 10 bp upstream (in the 5' direction of the coding strand) from the transcription start site (TSS), which is indicated as +1. By convention, all nucleotides upstream of the transcription initiation site (at +1) are numbered in a negative sense and are referred to as 5'-flanking sequences, while sequences downstream are numbered in a positive sense with the TSS as +1. Also by convention, the promoter DNA regulatory sequence elements such as the -35 and TATA box elements are described in the 5'–3' direction and as being on the coding strand. These elements function only in double-stranded DNA, however. Other transcriptional regulatory elements, however, can often act in a direction independent fashion, and such cis-elements are drawn accordingly in any schematic (see also Figure 36–8). Note that the transcript produced from this transcription unit has the same polarity or "sense" (ie, 5'–3' orientation) as the coding strand. Termination cis-elements reside at the end of the transcription unit (see Figure 36–6 for more detail). By convention, the sequences downstream of the site at which transcription termination occurs are termed 3'-flanking sequences.
  9. The primary transcript (pre-mRNA) is a precursor to the mRNA. The pre-mRNA is modified at both ends, and introns are removed to produce the mRNA. After processing, the mRNA is exported to the cytoplasm for translation by ribosomes.
  10. The process of synthesizing RNA from a DNA template has been characterized best in prokaryotes. Although in mammalian cells, the regulation of RNA synthesis and the processing of the RNA transcripts are different from those in prokaryotes, the process of RNA synthesis per se is quite similar in these two classes of organisms. Therefore, the description of RNA synthesis in prokaryotes, where it is best understood, is applicable to eukaryotes even though the enzymes involved and the regulatory signals, though related, are different
  11. The primary transcript is equivalent to the mRNA molecule. The mRNA codons on the mRNA are translated into an amino acid sequence by the ribosomes. Retroviruses
  12. Sigma factor needs to be released ---Re- and Un-winding activities -- Walk (literally) on the DNA 5’ to 3’ --growing RNA chain RNA polymerase binds both DNA template and growing RNA chain
  13. RNA polymerases I, II, and III. These enzymes catalyze the transcription of rRNA(Pol I), mRNA/miRNAs (Pol II), and tRNA and 5S rRNA (Pol III) encoding genes.
  14. Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA. They bind to the DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for many important cellular processes
  15. Formation of the basal transcription complex begins when TFIID binds to the TATA box. It directs the assembly of several other components by protein-DNA and protein-protein interactions; TFIIA, B, E, F, H, and polymerase II (pol II). The entire complex spans DNA from position –30 to +30 relative to the transcription start site (TSS; +1, marked by bent arrow).
  16. -TFIIF (together with the RNA Pol-II) --enzymatic activity (DNA-unwinding) -TFIIE --binds downstream regions -TFIIH (helicase activity) -TFIIJ --binds downstream regions
  17. Termination signal: specific DNA seq. -1000 to 2000 nucleotides Enzyme: Endonuclease --AAUAAA seq. --GU-rich seq. --poly(A) polymerase catalyzed the addition of 3’ poly(A) tail
  18. The cap structure is added to the 5' end of the newly transcribed mRNA precursor in the nucleus prior to transport of the mRNA molecule to the cytoplasm. The 5' cap of the RNA transcript is required both for efficient translation initiation and protection of the 5' end of mRNA from attack by 5' 3' exonucleases. The secondary methylations of mRNA molecules, those on the 2'-hydroxy and the N7 of adenylyl residues, occur after the mRNA molecule has appeared in the cytoplasm.
  19. Three of the 64 possible codons do not code for specific amino acids; these have been termed nonsense codons. These nonsense codons are utilized in the cell as termination signals; they specify where the polymerization of amino acids into a protein molecule is to stop. The remaining 61 codons code for the 20 naturally occurring amino acids
  20. The tRNA molecules serve as adapter molecules for the translation of mRNA into protein sequences. transfer RNAs (tRNAs) serve as the ultimate informational agents that decode the genetic code of mRNAs. tRNA contains single- and double-stranded regions. These spontaneously interact to produce 3-D structure.
  21. Cell cycle has two parts: growth and preparation (interphase) cell division mitosis (nuclear division) cytokinesis (cytoplasm division)
  22. In preparation for cell division, DNA is replicated and the chromosomes condense Each duplicated chromosome has two sister chromatids, which separate during cell division Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells.
  23. The steps of mitosis ensure that each new cell has the exact same number of chromosomes as the original
  24. Each duplicated chromosome appears as two identical sister chromatids joined together. The mitotic spindle begins to form. It is composed of the centrosomes and the microtubules that extend from them. The radial arrays of shorter microtubules that extend from the centrosomes are called asters (“stars”).
  25. Metaphase is the longest stage of mitosis, lasting about 20 minutes. The chromosomes convene on the metaphase plate, an imaginary plane that is equidistant between the spindle’s two poles.
  26. The centromere is a constricted region of the chromosome containing a specific DNA sequence, to which is bound 2 discs of protein called kinetochores. Kinetochores serve as points of attachment for microtubules that move the chromosomes during cell division:
  27. Anaphase is the shortest stage of mitosis, lasting only a few minutes. The two liberated chromosomes begin moving toward opposite ends of the cell, as their kinetochore microtubules shorten. Because these microtubules are attached at the centromere region, the chromosomes move centromere first (at about 1 µm/min).
  28. Two daughter nuclei begin to form in the cell.
  29. 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
  30. Healthy human cells are mortal because they can divide only a finite number of times, growing older each time they divide. Thus cells in an elderly person are much older than cells in an infant.
  31. Free radicals attack proteins and modify them. It usually disturbs protein function and can accelerate the aging process.
  32. Provide protection from enzymatic degradation and maintain chromosome stability Organization of the cellular nucleus by serving as attaching points to the nuclear matrix Allows end of linear DNA to be replicated completely They are called "molecular clock" of the cell. Cell division times are correlated with telomere length. After each cell division telomeres get shorter. When telomere shortens to the critical stage, the intensity of cell division significantly decreases, and then cell differentiates and ages. Telomeres are persistent in the not aging cells: cancer and germ line. Once the telomere shrinks to a certain level, the cell can no longer divide. Its metabolism slows down, it ages, and dies.