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Cell physio 202
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.
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.
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.
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
22. The Transcription Process
• Transcription is divided into
three steps for both
prokaryotes and eukaryotes.
They are:
1.Initiation
2. Elongation
3. 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
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
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.
47. GAU AUG CCG AGU CCA GGA UCU UGA
tRNA
UAC
tRNA
GGC
tRNA
UCA
tRNA
GGU
tRNA
CCU
tRNA
AGA
Methionine
Pro-
line
Serine Pro-line
Gly-
cine
Serine
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. CHROMOSOMES
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
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
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 µmVesicles
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
69. Proliferativecapacity
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
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
General schema by which genes control cell function.
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.
A twisted ladder with two long chains of alternating phosphates and sugars. The nitrogenous bases act as the “rungs” joining the two strands.
Complementary base pairs in DNA1.) Pyrimidine always pairs with purine2.) The higher number of hydrogen bonds in GC pairings confer sequence-specific annealing properties
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.
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.
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.
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.
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.
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
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
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
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.
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
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).
-TFIIF (together with the RNA Pol-II)
--enzymatic activity (DNA-unwinding)
-TFIIE
--binds downstream regions
-TFIIH (helicase activity)
-TFIIJ
--binds downstream regions
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
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.
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
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.
Cell cycle has two parts:
growth and preparation (interphase)
cell division
mitosis (nuclear division)
cytokinesis (cytoplasm division)
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.
The steps of mitosis ensure that each new cell has the exact same number of chromosomes as the original
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”).
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.
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:
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).
Two daughter nuclei begin to form in the cell.
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
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.
Free radicals attack proteins and modify them. It usually disturbs protein function and can accelerate the aging process.
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.