Apoptosis - programmed Cell Death
We will get a little bit technical below, no worries.. When we get into the LETTER SEQUENCES for the GENES, these are JUST designations pointing to the gene program.. sorta like names used to label CD's, purely arbitrary, and used for catelogging only
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Within the nucleus of the Cell, there are Chromosomes, or information packets containing further sets of instructions called GENES - which are made of/from DNA - we ARE made by the instructions from our GENES.. STEP by STEP.. From start to finish, the GENES have it all within them..
So our 3 key words are Chromosomes, GENES and DNA..
DNA - The DNA in one's cells is packaged into 46 chromosomes in the nucleus. As well as being a naturally helical molecule, DNA is supercoiled using enzymes so that it takes up less space.
Try holding a piece of string at one end, and twisting the other. As you add twist, the string creates coils of coils; and eventually, coils of coils of coils.
One's DNA is arranged as a coil of coils of coils of coils of coils! (TIGHT PACKING.)
This allows the 3 billion base pairs in each cell to fit into a space just 6 microns across.
If you stretched the DNA in one cell all the way out, it would be about 2m long and all the DNA in all your cells put together would be about twice the diameter of the Solar System. THERE ARE ONLY TWO STRANDS in DNA.
CHROMOSOME - In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46.
Twenty-two of these pairs, called autosomes, look the same in both males and females.
The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.
GENE - Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.)
The journey from gene to protein is complex and tightly controlled within each cell.
It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression.
NB: ALL ACTIONS to MAKE the body, keep it living, ARE CONTROLLED BY THE GENES.
GENES are sensitive to external AND internal chemical and electrical stimulation.
During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties.
The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. (Cytoplasm, the semi-liquid gel within the cell in which the nucleus resides).
Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm.
The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for one particular amino acid. (Amino acids are the building blocks of proteins.)
A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time.
Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid).
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The flow of information from DNA to RNA to Proteins is one of the fundamental principles of molecular biology.
Separation of GENES into FUNCTION -
Each cell expresses, or turns on, only a fraction of its genes.
The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation.
Gene regulation is an important part of normal development.
Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example.
Gene regulation also allows cells to react quickly to changes in their environments.
Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood.
Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA).
Signals from the environment or from other cells activate proteins called transcription factors.
These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription.
By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.
ONE ONLY wants a certain amount of muscles built, or skin built, or heart cells built at a given time.. WHEN DAMAGE occurs one wants some type of REPAIR to start, to enable the organ to continue to function properly..
Induction of Apoptosis:
There are GENES specifically designed to terminate or kill the cell. These are the killers..
There are specific categories, where attempts to repair damage happen first. When damage repair cannot be adequately accomplished the "death receptors" activate.
A cell has to normally TURN OFF the death sequence and a properly functioning cell WILL continually turn OFF its own death.. (Anti-Apoptosis genes). FOLLOW me on this.. The cell MUST continually TURN OFF its own death.. !!
When the cell cannot turn OFF its death cycle, which IS normally there, latent and waiting, due to excessive unrepairable damage to the DNA, the death receptors start to function to call up the steps needed to shut-down dna replication.. FLAGS appear to the other cells in the body responsible for cleaning up debris (damaged cellular material).
Death Domain Receptors: CRADD, FADD, TNF, TNFRSF10B (DR5).
DNA Damage: ABL1, CIDEA, CIDEB, TP53, TP73.
Extracellular Signals: CFLAR (CASPER), DAPK1, TNFRSF25 (DR3).
Other: BAD, BAK1, BAX, BCL10, BCL2L11, BCLAF1, BID, BIK, BNIP1, BNIP3, BNIP3L, CASP1 (ICE), CASP10 (MCH4), CASP14, CASP2, CASP3, CASP4, CASP6, CASP8, CD27 (TNFRSF7), CD70 (TNFSF7), DFFA, FAS (TNFRSF6), FASLG (TNFSF6), GADD45A, HRK, LTA (TNFB), NOD1 (CARD4), PYCARD (TMS1/ASC), TNFRSF10A, TNFRSF9, TNFSF10 (TRAIL), TNFSF8, TP53BP2, TRADD, TRAF3.
Anti-Apoptosis: AKT1, BAG1, BAG3, BAG4, BAX, BCL2, BCL2A1 (Bfl-1/A1), BCL2L1 (BCL-X), BCL2L10, BCL2L2, BFAR, BIRC3 (c-IAP1), BIRC6, BIRC8, BNIP1, BNIP2, BNIP3, BNIP3L, BRAF, CD27 (TNFRSF7), CD40LG (TNFSF5), CFLAR (CASPER), DAPK1, FAS (TNFRSF6), HRK, IGF1R, MCL1, NAIP (BIRC1), NOL3, RIPK2, TNF, XIAP (BIRC4).
Regulation of Apoptosis:
Negative Regulation: BAG1, BAG3, BAG4, BCL10, BCL2, BCL2A1 (Bfl-1/A1), BCL2L1 (BCL-X), BCL2L10, BCL2L2, BFAR, BIRC3 (c-IAP1), BIRC6, BIRC8, BNIP1, BNIP2, BNIP3, BNIP3L, BRAF, CASP3, CD27 (TNFRSF7), CD40LG (TNFSF5), CFLAR (CASPER), CIDEA, DAPK1, DFFA, FAS (TNFRSF6), IGF1R, MCL1, NAIP (BIRC1), NOL3, TP53, TP73, XIAP (BIRC4).
Positive Regulation: ABL1, AKT1, BAD, BAK1, BAX, BCL2L11, BCLAF1, BID, BIK, BNIP3, BNIP3L, CASP1 (ICE), CASP10 (MCH4), CASP14, CASP2, CASP4, CASP6, CASP8, CD70 (TNFSF7), CIDEB, CRADD, FADD, FASLG (TNFSF6), HRK, LTA (TNFB), NOD1 (CARD4), PYCARD (TMS1/ASC), RIPK2, TNF, TNFRSF10A, TNFRSF10B (DR5), TNFRSF25 (DR3), TNFRSF9, TNFSF10 (TRAIL), TNFSF8, TP53, TP53BP2, TRADD, TRAF2, TRAF3, TRAF4.
Both positive and negative regulation steps provide a type of ACTIVE FEEDBACK to keep the repair and killing mechanisms in balance.
It should be obvious that when the feedback mechanisms are set out of rhythm, that issues can arise.. It is in these feedback mechanisms where 'tampering' has happened, leading to a body "life span" at best on a programmed average of about 100 years.
I will get further into the specific gene sequences in the repair and regulatory genes later in the thread.
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