Hi teodora,
Thanks for posting your guide! :)
I thought it might be of some use if I were to add my* notes (*which I'll admit aren't technically mine as approx. one third is just copied and pasted with a few minor tweaks by yours truly ;)) on to elaborate on some concepts?
Mitosis
Spoiler
Cell growth stops at this stage and cellular energy is focused on the orderly division into two daughter cells or two daughter nuclei? . A checkpoint in the middle of mitosis (the Metaphase Checkpoint) ensures that the cell is ready to complete cell division.
More on Mitosis
Mitosis is a part of the cell cycle process by which chromosomes in a cell’s nucleus are separated into two identical sets of chromosomes, each in its own nucleus.
The stages of mitosis are: prophase, metaphase, anaphase, and telophase.
During mitosis, the chromosomes, which have already duplicated, condense and attach to fibers that pull one copy of each chromosome to opposite sides of the cell. The result is two genetically identical daughter nuclei. The cell may then divide by cytokinesis to produce two daughter cells.
Errors can occur during mitosis. One such error is multipolar mitosis, in which the wrong amounts of daughter cells areproduced. Other errors during mitosis can induce apoptosis (programmed cell death) or cause mutations. Certain types of cancer can arise from such mutations.
The Phases of Mitosis
Prophase
The complex of DNA and proteins contained in the nucleus, known as chromatin, condenses in preparation for division. Mitotic spindles also begin to form.
Metaphase
The cell’s chromosomes align themselves in the middle (or ‘equator’) of the cell.
There is a checkpoint between metaphase and anaphase, to ensure that the mitotic spindle has successfully attached to the centromeres of each chromosome, so that sister chromatids can be pulled apart during anaphase.
Unsure about the above (metaphase checkpoint)
Anaphase
Chromosomes split (into sister chromatids) and the sister chromatids move to opposite poles of the cell through a type of cellular “tug of war” in which spindle fibres are like ropes and the centrioles are like “teams”, who are tugging them apart.
Telophase
The sister chromatids reach opposite poles and the small nuclear vesicles in the cell begin to reform around the group of chromosomes at each end.
Proto-Oncogenes (Ras and Myc)
Spoiler
Proto-oncogenes produce protein products that normally enhance cell division or inhibit normal cell death. The mutated forms of these genes are called oncogenes.
Ras
Ras refers to a family of related proteins. All Ras proteins are involved in transmitting signals within cells (cellular signal transduction). When Ras is ‘switched on’ by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes which are involved in cell growth, differentiation and survival. As a result, mutations in ras genes can lead to the production of permanently activated Ras proteins. This can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals.
Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The three Ras genes in human (H-ras, K-ras, and N-ras) are the most common oncogenes in human cancer; mutations that permanently activate Ras are found in 20% to 25% of all human tumours and up to 90% of certain types of cancer (e.g., pancreatic cancer). For this reason, Ras inhibitors are being studied as a treatment for cancer.
Ras proteins function as molecular switches that control intracellular signaling networks. Ras-regulated signal pathways control such processes as actin cytoskeletal integrity, proliferation, differentiation, cell adhesion, apoptosis, and cell migration. Ras and ras-related proteins are often deregulated in cancers, leading to increased invasion and metastasis, and decreased apoptosis DOESN’T THAT MAKE RAS A TUMOUR SUPPRESSOR GENE?
Myc
c-Myc is a regulator gene that codes for a transcription factor. The protein encoded by this gene plays a role in cell cycle progression, apoptosis and cellular transformation.
Myc mutated in many cancers in a way such that it is persistently expressed. This leads to the unregulated expression of many genes, some of which are involved in cell proliferation, and results in the formation of cancer.
A common human chromosomal translocation involving Myc is critical to the development of most cases of Burkitt Lymphoma. Malfunctions in Myc have also been found in carcinoma of the cervix, colon, breast lung and stomach. Myc is thus viewed as a promising target for anti-cancer drugs.
Myc activation results in numerous biological effects. The first to be discovered was its capability to drive cell proliferation (by upgrading cyclins and down regulating p21), but it also plays a very important role in regulating cell growth (by upregulating ribosomal RNA and proteins), apoptosis (by downregulating Bcl-2), differentiation, and stem cell self-renewal. Myc is a very strong proto-oncogene and it is very often found to be upregulated in many types of cancers. Myc overexpression stimulates gene amplification, presumably through DNA over-replication.
A major effect of Myc is B cell proliferation.
Tumour Suppressor Genes (p53 and APC)
Spoiler
A tumour suppressor gene, or an anti-oncogene, is a type of gene that makes a protein called a tumour suppressor protein that helps control cell growth and protects a cell from one step on the path to cancer. Mutations in the DNA of this gene that cause a loss or reduction in its function can lead to cancer, usually in combination with other genetic changes.
Makes proteins that normally prevent cell division or cause cell death.
p53
p53 is a tumour suppressor protein and transcription factor that is altered in many forms of cancer. The gene tumour suppressor gene TP53 codes for p53. p53 has been described as "the guardian of the genome” because of its role in conserving stability by preventing genome mutation. The gene is the most frequently mutated gene (>50%) in human cancer, indicating that the TP53 gene plays a crucial role in preventing cancer formation
If a person inherits only one functional copy of the TP53 gene from their parents, they are predisposed (liable) to cancer and usually develop several independent tumours in a variety of tissues in early adulthood. This condition is rare, and is known as Li-Fraumeni syndrome. However, mutations in p53 are found in most tumour types, and so contribute to the complex network of molecular events leading to tumour formation.
In the cell, the p53 (transcription factor) protein binds to DNA, which in turn activates the production of a protein called p21 that interacts with a cell division-stimulating protein (cdk2). When p21 is complexed with cdk2 the cell cannot pass through to the next stage of cell division. Mutant p53 can no longer bind DNA in an effective way, and as a consequence the p21 protein is not made available to act as the 'stop signal ' for cell division. Thus cells divide uncontrollably, and form tumours.
In other words, p21 blocks the activity of a cyclin-dependent kinase that is required to proceed through G1. This ‘block’ allows time for the cells to repair the DNA before it is replicated. If the DNA damage is so extensive that it cannot be repaired, p53 triggers the cell to commit suicide. (IS THIS NECROSIS OR APOPTOSIS??)
The amount of information that exists on all aspects of p53s normal function and mutant expression in human cancers is now vast, reflecting its key role in the pathogenesis of human cancers. It is clear that p53 is just one component of a network of events that culminate in tumourformation.
APC
APC, or Adenomatous Polyposis Coli, is a tumour suppressor protein that is encoded by the tumour suppressor gene APC. Mutations in both copies of the APC gene can lead to familial adenomatous polyposis of the colon (FPC). The protein made by the APC gene plays a critical role in several cellular processes that determine whether a cell may develop into a tumour. The APC protein helps control how often a cell divides, how it attaches to other cells within a tissue, or whether a cell moves within or away from a tissue. This protein also helps ensure that the chromosome number in cells produced through cell division is correct. The APC protein accomplishes these tasks mainly through association with other proteins, especially those involved in cell attachment and signaling.
The APC protein is a negative regulator (meaning that it decreases the concentrations of) that controls Beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion.
E-cadherin, or epithelial cadherin, is a tumour suppressor gene that is involved in the cellular adhesion within a tissue. If E-cadherin loses function or expression, cancer cells acquire the capability of metastasis.
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. Beta catenin regulates the coordination of cell-cell adhesion and gene transcription.