Saturday, April 18, 2020

Genetic Control of Protein Synthesis,
Cell Function, and Cell Reproduction

Gene:-
• Located in cell nucleus
• Control heredity from parents to children
• Control functions of cells by determining synthesis of substances, structures, enzymes & chemicals
• Composed of DNA
• Controls RNA formation which in turn controls protein synthesis

Gene Expression:-
The entire process from transcription of genes to translation of RNA and formation of proteins.
• 30,000 different genes form different proteins
• RNA (transcribed from same gene) is processed into different versions for alternate forms of a proteins
• 100,000 types of proteins are produced in body
• Proteins with other biomolecules form cellular organelles
• Some proteins are enzymes that catalyze chemical reactions & synthesize chemicals (Glycogen, ATP,etc).



》Genes Control Protein Synthesis
DNA:- A long double stranded helical molecule with end to end attached genes.

Building blocks of DNA:

(1) phosphoric acid
(2) a sugar (deoxyribose)
(3) four nitrogenous bases
(2 Purines=A-G & 2 Pyrimidines=T-C).

Phosphoric acid and Deoxyribose form two helical strands (backbone) and Bases (attached to Deoxyribose) lie b/w two strands and connect them.





Nucleotides:-
A single molecule of Phosphoric Acid, Deoxyribose and a base forms an acidic Nucleotide.
• 4 types depending on base
1) Deoxyguanylic
2) Deoxyadenylic
3) Deoxcytidylic
4) Deoxythymidylic




=> Nucleotides form DNA
• Form two DNA strands held together by weak cross linkages (Loose bonds or Hydrogen Bonds)
• Two strands can easily be pulled apart due to loose bonds
• Phosphoric acid and Deoxyribose form two helical strands (backbone) and Bases (attached to Deoxyribose) lie b/w two strands and connect them.
• Chargaff Rules:
1) Adenine bonds with Thymine
2) Guanine bonds with Cytosine
Simply=>Purines bond with Pyrimidines
A-T has two Hydrogen Bonds
G-C has three Hydrogen Bonds
• Ten pairs in each helix turn
=>Genetic Code (A code word):-
Genetic code enables DNA to control protein synthesis
• After splitting of strands bases appear and form genetic code
• Successive triplet of bases
• Control amino acid sequence in a protein
e.g. GGC, AGA, CTT (Separated by Arrows in the figure)


Each nucleotide is oppositely transcribed.
GGC, AGA, CTT
CCG, UCU, GAA



CCG codes for Proline,
UCU codes for Serine,
GAA codes for Glutamic Acid.


=》Transcription
Def: The process in which RNA is formed from DNA by code transfer.

• RNA from nucleus diffuses through nuclear pores into cytoplasm and controls protein synthesis
• The DNA in nucleus controls celluar functions in cytoplasm by RNA
=>Mechanism
• Synthesized in nucleus from DNA template
• DNA strands separate and one is used as a template
• Genetic Codes in DNA form codons (Complementary Genetic Codes) in RNA which control amino acid sequence in a protein
Basic Building Blocks of RNA.
Building blocks of RNA are similar to DNA except two things:-
RNA contains Ribose (with extra OH group) instead of Deoxyribose and Uracil instead of Thymine.

Formation of RNA Nucleotides.
The nucleotides containing bases Adenine, Guanine, Cytosine and Uracil instead of Thyamine are synthesized.

“Activation” of the RNA Nucleotides.
• Activated by RNA polymerase
• Two phosphates attach to right side nucleotides to form triphosphates with high energy phosphate bonds
• Energy becomes available for addition of new RNA nucleotides to RNA chain
Assembly of RNA Chain.
• Assembled by RNA polymerase
• RNA polymerase recognizes and attaches to promoter (Sequence of nucleotides ahead of gene to be transcribed).
• RNA polymerase unwinds and separates two turns of DNA helix
• RNA polymerase adds new activated RNA nucleotides to the RNA chain by following method
-> Forms a hydrogen bond b/w end base of DNA strand & base of RNA nucleotide in nucleoplasm
-> RNA polymerase breaks two of three phosphates in RNA nucleotides releasing energy for formation of covalent linkage b/w remaining phosphate of RNA nucleotide and end ribose of growing RNA chain.
-> RNA polymerase reaches chain-terminating sequence and separates RNA chain from DNA strand
-> DNA strands rebond and RNA chain is released into nucleoplasm
• Ribose and Deoxyribose bases combine in following manner



=> Types of RNA
Perform different functions
• Synthesize proteins
• Control gene regulatory functions
• Control post transcriptional RNA modifications
1. Precursor Messenger RNA (Pre-mRNA)
• Large & immature RNA
• Processed to form mature mRNA
• Contains two segments
i) Introns
->Removed by splicing

ii)Exons
->Retained in final mRNA

2. Small Nuclear RNA (snRNA)
• Directs splicing of Pre-mRNA to form mRNA
3. Messenger RNA (mRNA)
• Carries genetic code of a protein to cytoplasm
4. Transfer RNA (tRNA)
• Transports amino acids to ribosomes for protein assembly
5. Ribosomal RNA (rRNA)
• Forms 75 types of proteins
• Place of protein assembly
6. MicroRNA (miRNA)
• Consists of 21 to 23 nucleotides
• Regulates gene transcription & translation.
=》 Messenger RNA (The Codons)
• Single stranded & Suspended in cytoplasm
• Consist of hundred/thousand nucleotides
• Contains codons
e.g.
CCG codes for Proline,
UCU codes for Serine,
GAA codes for Glutamic Acid.

List of 22 Common Amino Acid (AA) Codons for Protein Synthesis
• Most AAs have more than 1 codons
• Single start codon for Chain Initiation
• Three stop codons for Chain Termination


=》 Transfer RNA (tRNA)
• Contains Anti-Codon
-> Triplet of nucleotide bases
-> Specific for a particular mRNA codon
(i,e; Anti-codon with GGG bases is specific for Codon with CCC bases)
-> Located below mid of molecule
• Plays essential role in protein synthesis because transfers amino acids to ribosomes
• 20 specific tRNAs exist for carrying 20 specific amino acids to ribosomes for protein synthesis .
• Recognizes specific mRNA codon in ribosomes and delivers amino acid at exact place of protein chain
• A small molecule with 80 nucleotides in a folded chain similar to cloverleaf.
• Amino acid attaches to OH group of ribose in adenylic acid.
• During Protein Synthesis
-> Anticodon bases combine with mRNA codon bases.
-> Amino acids line up one after another along mRNA chain establishing exact amino acid sequence in protein chain.



=》RIBOSOMAL RNA (rRNA)
• Ribosome
-> Composed of
> RNA (60%)
> Protein (40%)
- 75 types of protein
- Both structural proteins and enzymes
-> Physical manufacturing plant for protein synthesis
-> Functions with
> tRNA
- Transfers amino acids to ribosomes
> mRNA
- Provides information for sequencing amino acids in protein chain
-> Synthesis
> Occurs in nucleolus.
> rRNA synthesis genes are found in five chromosome pairs
> After synthesis rRNA collects in nucleolus
- Structure lying near chromosomes
- Size inc with inc. protein synthesis due to rRNA accumulation
- Processes rRNA by combining with ribosomal protein to form granular condensation products
_ Primordial ribosomal subunits
_ Move to cytoplasm by nuclear pores where assemble to form mature ribosomes.
_ Proteins form in cytoplasm not in nucleus because nucleus lacks mature ribosomes

=》Micro RNA (miRNA)
• Short (21 to 23 nucleotides) single-stranded RNA fragments
• Regulate gene expression
• Transcribed from DNA genes but not translated to proteins and are called non-coding RNA.
• Processed by cell into molecules complementary to mRNA that decrease gene expression
• Generation of miRNAs:-
-> Pri-miRNAs
> Longer primary precursor RNAs
> Primary gene transcripts
> Undergo processing in nucleus by microprocessor complex to pre-miRNAs
-> Pre-miRNAs
> 70-nucleotide stem-loop structures
> Undergo processing in cytoplasm by dicer enzyme to RISC (RNA-induced silencing complex) and miRNAs
• Function
-> Regulates gene expression by binding to complementary region of RNA and promoting repression of translation or degradation of mRNA before ribosomal translation.
-> miRNA alterations result in cancer and heart diseases


=》Small Interfering RNA (siRNA) (Synthetic miRNA / Silencing RNA / Short interfering RNA)
• A type of miRNA
• Short, double-stranded, 20-25 nucleotides
• Interfere with specific genes expression
• Administered to silence specific genes expression
• Avoids nuclear processing by microprocessor complex and enters cytoplasm where activates RISC silencing complex that blocks mRNA translation.
• Tailored for any specific gene sequence and block translation of any mRNA and repress expression by any gene for which nucleotide sequence is known.
• Researchers have proposed that siRNAs may become useful therapeutic tools to silence genes that contribute to pathophysiology of diseases.


=> Translation:-
• Protein formation process on ribosomes
• mRNA travels through ribosome beginning at “chain-initiating” (start) codon till "chain-terminating" (stop) codon.
• After start codon, ribosome reads amino acid codons and forms a specific protein then releases protein into cytoplasm after stop codon.
• Polyribosomes:
-> A cluster of 3-10 ribosomes attached at a time to an mRNA
-> mRNA
- Forms protein in several ribosomes at a time
- Initial end passes to successive ribosomes after leaving first.
- Has no specificity for ribosomes

• Ribosomes Attach to ER
-> Amino Acids in initial ends of forming protein attach to specific receptor sites on ER then enter ER matrix resulting in granular appearance during protein synthesis
-> Translation occurs in several ribosomes at a time in an mRNA.
-> Protein chains pass through ER membrane to ER matrix.
-> Except glandular cells which form protein-containing secretory vesicles while other cell ribosomes release proteins (Enzymes+Structural) in cytosol instead of ER

• Chemical Steps in Protein Synthesis
1. Each amino acid is activated by a chemical process in which ATP combines with amino acid to form an AMP complex with amino acid, giving up two high-energy phosphate bonds.

2. Activated amino acid combines with specific tRNA to form an amino acid-tRNA complex and releases AMP.

3. Amino acid-tRNA complex approaches mRNA molecule in ribosome. tRNA anticodon attaches to specific mRNA codon and lines up amino acid in appropriate sequence to form a protein molecule.

Peptidyl transferase (Ribosomal protein), forms peptide bonds between amino acids in protein chain. This requires two phosphate bonds making a total of 4 bonds used for each amino acid added to protein chain. So, protein synthesis is energy consuming.

• Peptide Linkage
OH is removed from COOH of one amino acid and H+ is removed from NH2 of other amino acid which combine to form water while remaining two reactive sites of C- and -N bond with each other to form peptide linkage.



=》 SYNTHESIS OF OTHER SUBSTANCES IN CELL
After synthesis, proteins (as enzymes) control almost all cellular reactions including synthesis of CLN that have other cell functions.

==》CONTROL OF GENE FUNCTION AND
BIOCHEMICAL ACTIVITY IN CELLS
• Genes control both physical and chemical functions of cells.
• Gene activation degree is controlled by at least one Internal Feedback Control otherwise cell parts overgrow and reactions over-act until cell death.
• Approx. 30,000 genes exist.
• Two methods of control for Cell Biochemical Activity:
-> (1) Genetic regulation:-
In which gene activation degree and gene product formation are controlled.
-> (2) Enzyme regulation:-
In which enzyme activity levels are controlled.

=》GENETIC REGULATION
( Regulation of gene expression)
"It is regulation of transcription in nucleus and translation in cytoplasm."
• Provides ability to respond to environmental changes
• Forms different types of cells, tissues, and organs (Differential Regulation)
• Allows different cell types to perform their specific functions.
• As cardiac myocyte contains same genetic code as renal tubular cell but genes expressed in cardiac myocyte are not expressed in renal tubular cell.
• Decides production and quantity of gene products (Proteins)
• Occurs at any point in transcription, RNA processing, and translation
• Promoter Controls Gene Expression.
-> Protein synthesis starts with transcription of DNA into RNA which is controlled by regulatory elements found in gene promoter


-> Basal promoter
> Found in protein-coding genes
> Binding site for RNA polymerase 2 that travels DNA to synthesize RNA
> Consists of seven bases (TATAAAA) called TATA box
- Binding site for TATA-binding protein, transcription factor IID complex and transcription factor IIB binds to both DNA and RNA polymerase 2

-> Upstream Promoter
> Located upstream from transcription start site
> Contains binding sites
- For +ve/-ve TFs that can affect transcription by interacting with basal promoter proteins
- Vary from gene to gene so give different gene expressions in different tissues.

-> Enhancers :-
> Affect transcription
> Bind TFs
> Located away from gene of action like
- On a different chromosome
- Upstream or downstream of gene
> Relatively close in coiled DNA
> 110,000 in human genome

-> Gene Separation:-
> Active genes (transcribing genes) from repressed genes.
> Difficult because of close occurrence of genes
> Achieved by chromosomal insulators

-> Insulators :-
> Gene sequences that provide a barrier to a gene against transcriptional influences from surrounding genes
> Vary in DNA sequences & binding proteins
> Modulated by DNA methylation
- e.g. Mammalian insulin-like growth factor 2 (IGF-2) gene.
- In which Mother’s allele has an insulator,
between enhancer and promoter, that allows binding of a transcriptional repressor.
- But, Paternal DNA sequence is methylated so transcriptional repressor cannot bind to insulator and IGF-2 gene is expressed from paternal copy of gene.



• Other Mechanisms of Promoter for Controlling Transcription
~ These are variations in basic mechanism of Promotor Control

1. Controlled by TFs located elsewhere in genome. Regulatory gene forms regulatory protein that acts either as an
activator or a repressor of transcription.

2. Different promoters are controlled at a time by a regulatory protein. At times regulatory protein acts as an activator for one promoter and as a repressor for another promoter.

3. Control can occur
-> At Start of transcription on DNA strand
-> At mid of transcription on DNA strand
-> During processing of RNA molecules in nucleus
-> During RNA translation by ribosomes

4.
-> In nucleated cells, nuclear DNA is packaged in specific structural units called chromosomes.
-> DNA within chromosome is wound around small proteins called histones, which are held tightly in a compacted state by some other proteins.
-> DNA cannot form RNA in compacted state.
-> Some control mechanisms decompact a portion at a time for partial RNA transcription.
-> Specific TFs control transcription rate by chromosomal promoters
-> Higher control orders establish proper cell function.
-> Outside cell signals (e.g. Hormones) activate specific chromosomal areas and specific TFs so control chemical machinery for cell function.

-> Large no. of genetic activity control is because of large no. of genes (30,000) in human cell.
-> Gene control systems control intracellular quantity of amino acids, amino acid derivatives, and intermediate substrates and products of carbohydrate, lipid, and protein metabolism.


=》CONTROL OF INTRACELLULAR FUNCTION BY ENZYME REGULATION
• Inhibitors or activators act on enzymes and control cell activities
• Second category of control mechanisms
• Enzyme Inhibition
-> Some substances (Inhibitors) inhibit specific enzyme systems that synthesize them.
-> Act on first enzyme in the sequence by binding on allosteric site and causing conformational change that inactivates enzyme
-> First enzyme inactivation prevents buildup of intermediary products
-> A negative feedback control
-> Controls quantities of amino acids, purines, pyrimidines, vitamins, and other substances

• Enzyme Activation
-> Inactive enzymes activate on demand
~ ATP Concentration
-> When ATP decreases in cell then breaks down into cAMP (Activator) that activates phosphorylase which splits glycogen into glucose that is metabolized and energy is used for ATP synthesis.
-> Thus, ATP conc. is regulated in cell

~ Purine and Pyrimidine Conc.
-> Purines and pyrimidines are needed in equal quantities for forming DNA and RNA
-> Purines form and inhibit their own enzymes but activate pyrimidine enzymes
-> Pyrimidines form and inhibit their own enzymes but activate purine enzymes
-> Thus, equal amounts of purine and pyrimidine form in cell

=》Summary
• Two principal control mechanisms for quantities of cellular constituents:
(1) Genetic regulation
-> Activates or inhibits genes
-> Feedback control system that monitors and corrects composition of cell
(2) Enzyme regulation
-> Activates or inhibits enzyme systems
-> Feedback control system that monitors and corrects composition of cell
• Hormones control by activating or inhibiting one or more intracellular control systems.


==》CELL REPRODUCTION
• Controlled by DNA–GENETIC SYSTEM
-> Determines growth & division of cells
-> Controls developmental stages of human from single cell fertilized ovum to whole functioning body
-> Central theme of life

=》Life Cycle of the Cell
• Period from one cell reproduction to next cell reproduction
• 10-30 hours in non-inhibited cells
• Terminated by Mitosis
-> Forms two daughter cells
-> 30 minutes
• Interphase
-> Interval between mitosis
-> 95 percent of life cycle
• Exceptional Conditions
-> Inhibitory factors slow or stop life cycle of cell so it varies from 10 hours (bone marrow cells) to entire life (nerve cells).

=》 Replication of DNA
• First step of cell reproduction in nucleus
• Duplication of DNA in chromosomes
• Followed by mitosis after 1-2 hour period of preliminary mitotic changes
• Starts 5-10 hours before mitosis while takes 4-8 in completion
• Forms two exact replicas of DNA that will be part of two daughter cells of mitosis
• Replication Events :-
Mostly same as RNA transcription except a few changes like
-> Both strands replicate instead of one
-> Entire strands replicate instead of small portions
-> Carried by DNA polymerase that attaches to and moves along DNA template strand while DNA ligase attaches new DNA nucleotides to one another by using high-energy phosphate bonds
-> DNA first forms in segments which then merge by DNA ligase
-> New strand remains attached to original strand and are coiled together.
-> Chromosome contains million DNA helixes each with 6cm length so cannot uncoil except for special mechanisms. Enzymes cut each helix, separate segment by rotation then resplice helix. Thus, two new helixes become
uncoiled.

• DNA “Proofreading” (DNA Repair)
-> 1 hour period between replication and mitosis
-> The process in which inappropriate DNA nucleotides are removed and replaced by appropriate complementary nucleotides with the help of DNA polymerases and DNA ligases is called DNA Proofreading.
• “Mutation” :-
-> Abnormality in transcription process.
-> Reduced by DNA Proofreading
-> Results in abnormal protein formation that leads to abnormal cell function and even cell death
-> 30,000 genes exist in human genome
-> Period between two human generations is 30 years in which 10 mutations can occur in passage of genome from parent to child
-> But protected by two chromosomal sets with identical genes so one functional gene is available to child despite mutations

• CHROMOSOME (AND THEIR REPLICATION)
-> Contains DNA helixes
-> 46 (23 Pairs) in human cell
-> Pair contains identical genes & may contain different genes
-> Contains histone proteins
> electropositively charged small & bobbin-like cores on which DNA helix coils
> Regulate DNA activity by tight packaging so DNA cannot form RNA or new DNA
> Regulatory proteins decondense histone packaging and allow RNA formation
-> Contains non-histone proteins
> Act as chromosomal structural proteins and as activators, inhibitors, and enzymes
-> Replication:-
> Occurs after a few minutes of DNA replication.
> New DNA helixes collect new protein molecules
> Two chromosomes (Chromatids) remain attached at centromere until mitosis

=》CELL MITOSIS
• The cell division in which two daughter cells with diploid number of chromosomes are formed
• Chromosomes replicate to form two chromatids followed by mitosis after 1-2 hours
• Mitotic Apparatus :-
-> Centrioles :-
> Two pairs lying close to each other near one pole of nucleus.
> Replicate before DNA replication
> Small cylindrical bodies with 0.4 ųm length & 0.15 ųm in diameter
> Consist of nine parallel tubules arranged as a cylinder
> In a pair lie at right angles to each other
> Centrosome = A pair of centrioles with Pericentriolar material
> Move apart due to growth of microtubule proteins between them called Spindle
> Some microtubules grow away from centriole pairs like a spiny star called Aster whose spines penetrate nuclear membrane and separate chromatids during mitosis
> Entire set of microtubules and two pairs of centrioles are called mitotic apparatus
• Prophase
-> First stage of mitosis
-> Spindles form
-> Chromosomes condense
• Prometaphase
-> Aster spines fragment nuclear membrane
-> Aster microtubules attach to chromatids at centromeres then in a later stage pull them to cellular poles
• Metaphase:-
-> Both aster microtubular spines push each other at mitotic spindle (where they interdigitate) by molecular motors.
> Minute contractile actin proteins extend between spines
> Slide spines in reverse direction
> So, by attached microtubules, pull chromatids to cell center that line up to form equatorial plate
• Anaphase:-
-> 46 pairs of chromatids are pulled apart that form separate sets of 46 chromosomes on each pole mitotic aster
• Telophase:-
-> Chromosome sets are completely pushed apart then mitotic apparatus dissolves
-> Nuclear membrane develops from ER
-> Contractile ring of microfilaments (actin & myosin) between two nuclei pinches cell into two daughter cells

=》CONTROL OF CELL GROWTH AND CELL REPRODUCTION
• Some cells grow and reproduce all time e.g.
(1) Blood-forming cells of bone marrow
(2) Germinal layers of skin
(3) Epithelium of gut
• Some cells may not reproduce for many years e.g. Smooth muscle cells
• Some cells do not reproduce during entire life of a person, except during fetal life. e.g. Neurons and striated muscle cells
• In some tissues, cells grow and reproduce after insufficiency like e.g.
-> After surgical removal of 7/8 of liver causes remaining 1/8 to grow into normal mass.
-> Glandular cells, bone marrow, subcutaneous tissue, intestinal epithelium except nerve and muscle cells.
• Cell number maintaining mechanisms are still poorly understood
• Three ways control growth
1)
• By growth factors that originate in adjacent tissues or other body parts & circulate in blood
e.g. Some gland epithelial cells (like pancreas) get growth factor from underlying Connective Tissue.

2)
• Insufficient space inhibits cell growth
e.g. Cells in a tissue culture grow until they contact a solid object then growth stops.

3)
• Cells in a tissue culture stop growing when their secretions collect in culture medium. It is a negative feedback control
• Telomeres
-> A region of repetitive nucleotide sequences located at each end of a chromatid
-> Protective caps that prevent chromosomal degradation during cell division
-> Disposable chromosomal buffer
-> “Primer” RNA does not attach to very end of DNA and starts replication after missing a small DNA part so copied DNA loses additional nucleotides from telomere region without which genomes lose information after each cell division.
-> 8000 base pairs at birth to 1500 base pairs in old age in blood cells
-> Lose 30-200 base pairs/cell division
-> Shorten to a critical length, chromosomes become unstable and cells die
-> Add to physiological changes of aging.
-> May erode because of oxidative stress and inflammatory diseases
-> Get additional bases by Telomerase in some cells like stem cells of bone marrow & skin, germ cells of ovaries and testes.
-> Cells with low telomerase activity inherit defective chromosomes, become senescent (old) and cease dividing.
-> Regulate cell proliferation and maintain gene stability
-> Cancer cells have high telomerase activity that maintains telomere length even after uncontrollable proliferation
-> Shortening protects from cancer and other proliferative diseases

• Regulation of Cell Size
-> Determined by amount of DNA in nucleus
-> If no replication occurs, size will be normal & constant
-> Chemical Colchicine prevents mitotic spindle formation and mitosis despite continued DNA replication
-> So, DNA quantity rises which forms more RNA that forms more protein, ultimately cell grows larger.

==》CELL DIFFERENTIATION
• Property of cell growth and cell division
• "Changes in physical and functional properties of cells as they proliferate in embryo to form different bodily structures and organs"
• Experiment
-> When nucleus from an intestinal mucosal cell of a frog is surgically implanted into a frog ovum from which original ovum nucleus was removed, result is formation of a normal frog.
-> So a differentiated cell carries all genetic information for development
• Occurs due to selective repression of different gene promoters
• Some DNA helix portions wound around histone cores condense and no longer uncoil to form RNA molecules
• Cellular genome produces a regulatory protein that forever represses a select group of genes
• Mature human cells produce less proteins (8000-10,000) than total number of genes (30,000) in cell.
• In embryo adjacent cells control differentiation e.g.
-> Primordial chorda-mesoderm
(Primary Organizer)
> Forms a focus for embryo development
> Differentiates into a mesodermal axis that contains somites and forms body organs due to adjacent tissue inductions
-> Eye vesicles (Induction)
>Approach head ectoderm
>Thicken ectoderm into lense plate that folds inward to form eye lense

==》APOPTOSIS
• "Programmed (suicidal) cell death"
• Body contains 100 trillion cells (organized community) regulated by rate of cell division and cell death otherwise tissues shrink or grow excessively
• When cells become useless or threat to organism then undergo apoptosis.
• Cells do not spill contents so adjacent cells remain healthy
• Occurs in tissues that remodel during development
• In intestine and bone marrow billions of cells die each hour and replaced by new cells
• Mechanism:
Apoptosis initiates when procaspases activate into caspases (proteases) that cleave and activate other procaspases which triggers a proteolytic cascade that condenses cell by disassembling cytoskeleton and alters cell surface so macrophage attaches and digests cell
• Abnormalities result in neurodegenerative diseases (Alzheimer disease), cancer and autoimmune disorders
• Induced in cancer cells by some drugs

==》Necrosis
• Injured cell death due to swelling and bursting of fragile membrane
• Cells spill contents that inflame & injure adjacent cells

==》CANCER
• Due to mutation or abnormal activation of genes that control cell growth and mitosis.
• Proto-oncogenes:-
-> Normal genes
-> Control cell adhesion, growth, and vision
-> After mutation or excess activation become oncogenes that
> Function abnormally
> Cause cancer
> 100 types
• Tumor Suppressor Genes
(Anti-Oncogenes)
-> Suppress activation of specific oncogenes
-> Loss or inactivation activates oncogenes that lead to cancer
• Fewer cells become cancerous after mutation because (Factors decreasing cancer chances)
1)
Most Mutated cells die

2)
Few survived mutated cells become cancerous because of feedback control

3)
-> Cancerous cells are destroyed by immune system.
-> Mutated cells form abnormal proteins (because of abnormal genes) that stimulate immune system for formation of antibody or lymphocytes that react and destroy cancerous cells.
-> Suppressing immune system by taking drugs after kidney or heart transplantation increases cancer chances by fivefold.

4)
-> Different oncogenes at a time cause cancer
e.g. A gene promoting rapid production of a cell will not produce cancer because a gene for blood vessel formation is absent at the same time.






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