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Introduction
In 1858 the pathologist Rudolph Virchow coined the cell doctrine which states that "When a cell arises, there must have been a previous cell, just as animals can only arise from animals and plants from plants."
Cells are generated from cells and the only way to make more cells is by division of those that already exists. Repeated cycles of cell growth and division result in development of a single fertilized egg into the more than 103 cells that make up the human body.
Introduction
Definition: It is process by which cell reproduces by performing an orderly sequence events in which it duplicates its contents and then divides into two.
State
Phase
Abbreviation
Description
A resting phase where the cell has left the cycle and has stopped dividing.
Cells increase in size in Gap 1..
Quiescent/ senescent
Gap 0 Gap 1
G0 G1 S G2
Interphase
Synthesis Gap 2
Cell division
Mitosis
Gap 1-phase
The first phase within interphase, 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, which had been considerably slowed down during M phase, resume at a high rate. This phase is marked by synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication. Duration of G1 is highly variable, even among different cells of the same species.
S-phase
S phase starts
when DNA synthesis commences; When it is complete, all of the chromosomes have been replicated, i.e., each chromosome has two (sister) chromatids. Thus, during this phase, the amount of DNA in the cell has effectively doubled. It is the longest phase of the cell cycle.
G2 -phase
G2 phase, which lasts until the cell enters mitosis. Again, significant biosynthesis occurs during this phase, mainly involving the production of microtubules, which are required during the process of mitosis. Inhibition of protein synthesis during G2 phase prevents the cell from undergoing mitosis.
Mitosis
Stages of Mitosis
1.Prophase The chromosomes gradually condense and appear as strands that become thicker and shorter; - The nuclear envelope breaks up. 2.Metaphase The chromosomes are condensed; - A mitotic spindle is formed of microtubules; - Microtubules attach to the centromeres on chromosomes and to the centrioles at opposite poles of the cell 3.Anaphase The chromatids separate and move to opposite poles 4.Telophase The chromatids are at opposite poles of the cells - The nuclear envelope is formed 5.Cytokinesis Division of the cytoplasm mediated by actin filamen
In humans
The proliferation of cells is similarly regulated in G1 phase by a decision point analogous to START called as RESTRICTION POINT. In the presence of appropriate growth factors cell pass this point and enter S phase. In the absence of growth factors the cells enter into G0 phase.
REGULATION OF Cdks
Cdk inhibitors(CKI)
Active complexes of cyclins and CDKs exert their biological effects by phosphorylating proteins During the G1 phase, a major target of cyclin/CDK complexes is the retinoblastoma protein (pRb).
pRb
When pRb is in the dephosphorylated form, during the G0 phase and early in the G1 phase, it is active . pRb exerts its growth-suppressing effects by binding to many cellular proteins, including the transcription factors of the E2F family E2F transcription factors regulate the expression of numerous genes that are expressed during G1, or at the transition from the G1 to the S phase, to initiate DNA replication. pRb that is bound to an E2F transcription factor inhibits the transcription factor's activity. Following phosphorylation by cyclin/CDK complexes, pRb dissociates from E2F, allowing the transcription factor to bind DNA sequences and activate the expression of genes necessary for the cell to enter the S phase.
p53
The p53 protein senses DNA damage and can halt progression of the cell cycle in G1 (by blocking the activity of Cdk2 Under normal circumstances p53 levels remain very low due to its interaction with a member of the ubiquitin ligase family called MDM2. The p53 protein is also a key player in apoptosis, forcing "bad" cells to commit suicide. So if the cell has only mutant versions of the protein, it can live on perhaps developing into a cancer. More than half of all human cancers do, in fact, harbor p53 mutations and have no functioning p53 protein. An extreme case of this is Li Fraumeni syndrome, where a genetic a defect in p53 leads to a high frequency of cancer in affected individuals. A genetically-engineered adenovirus, called ONYX-015, can only replicate in human cells lacking p53. Thus it infects, replicates, and ultimately kills many types of cancer cells in vitro. Clinical trials are now proceeding to see if injections of ONYX-015 can shrink a variety of types of cancers in human patients.
Applied physiology
Deregulation of cell cycle control proteins plays a key role in the development of cancer.
Overactivation of proteins that favor cell cycle progression, namely cyclins and CDKs, and the inactivation of proteins that impede cell cycle progression, such as CKIs, can result in uncontrolled cell proliferation.
ATM
ATM (="ataxia telangiectasia mutated") gets its name from a human disease of that name , whose patients are at a greatly increased (~100 fold) risk of cancer. The ATM protein is involved in detecting DNA damage, especially doublestrand breaks; interrupting (with the aid of p53) the cell cycle when damage is found; Maintaining normal telomere length. It is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease.
Telomerase
Human telomerase present at very low levels, in most normal cells and tissues, but that during cancer progression, telomerase is abnormally reactivated in all major cancer types. while telomerase does not cause cancer, the continued presence of telomerase enables cancer cells to maintain telomere length, providing them with indefinite replicative capacity. It has been shown in various tumor models that inhibiting telomerase activity results in telomere shortening and causes aging or death of the cancer cell. Development of anti-cancer therapies based on telomerase inhibitors and telomerase therapeutic vaccines
CANCER TREATMENT
Chemotherapy of cancers is aimed towards interrupting the cell cycle and preventing the cancer cells from proliferating. As a side effect, however, also the normal sites of cell proliferation are affected resulting in hair loss, intestinal disorders, anaemia and infertility.
Anticancer drugs
Some cytostatic drugs act on the S phase and inhibit DNA synthesis Methotrexate Fluorouracil Mercaptopurine Some cytostatic drugs cause cells to accumulate in G2 Mitomycin C Adriomycin Cyclophosphamide
ANTICANER DRUGS
VINCA ALKALOIDS(mitotic inhibitors)
Vincristine Vinblastin (bind to the microtubular protein TUBULIN and prevents its polymerization,disruption of cyotoskeleton)
Psoriasis
rapid proliferation of skin cells, which divide up to 1,000 times faster than normal. In normal cells, high cGMP levels makes cells divide faster, while high cAMP levels slow down cell division. Individuals with psoriasis have both high cGMP and low cAMP levels, causing the cells to replicate abnormally fast. This imbalance results in a tremendous increase in cell division.
REFERENCES
THE CELL- Geoffrey. M .Cooper Molecular Biology Of CellBruce,Alexender,Lewis,Marin,Roberts,Peter GRAYS Human Anatomy HUMAN physiology-FOX HUMAN PHYSIOLOGY-Rhoades Internet
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