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Cancer biology FAQ!
- What is an oncogene?
- What is a proto-oncogene?
- What is a tumour suppressor gene?
- What is the cell cycle?
- What are cyclins?
- When are cell cycle checkpoints?
An oncogene is a sequence of deoxyribonucleic acid (DNA) that has been altered or mutated from its original form, the proto-oncogene.
Operating as a positive growth regulator, the proto-oncogene is involved in promoting the differentiation and proliferation of normal cells. A variety of proto-oncogenes are involved in different crucial steps of cell growth, and a change in the proto-oncogene's sequence or in the amount of protein it produces can interfere with its normal role in cellular regulation. Uncontrolled cell growth, or neoplastic transformation, can then ensue.
The term "proto-oncogene" was coined to distinguish the normal gene from its altered form "oncogene". The resulting nomenclature is somewhat misleading.
The tumour suppressor genes in a healthy cell work together with another class of genes, called proto-oncogenes, to control cell reproduction. Tumour suppressor genes code for proteins that restrain cell growth, and proto-oncogenes specify proteins that stimulate cell growth. Mutations in either type of gene can disrupt the delicate balance between inhibition and activation of the molecular processes that regulate a cell's life cycle, leading to the uncontrolled cell growth characteristic of cancer. A mutation in one gene alone does not cause a malignant tumour to develop; a number of genetic insults occurring in a few different genes over time are necessary for a cell to undergo transformation to a malignant state. For example, a proto-oncogene becomes a cancer-causing oncogene (q.v.) when mutated in a manner that increases the cell's propensity to divide excessively. In order for a cell to give rise to cancer, other mutations, such as damage to a tumour suppressor gene, must arise.
For a eukaryotic somatic cell to divide in two it has to go through a series of steps. These steps constitute the cell cycle.
- Interphase: 3 stages-
- G1: 46 chromatids.
- S: 46 PAIRS of chromatids (i.e. 92).
- G2: 2 chromatids join at centromere (become chromosomes); + centrioles duplicate.
- Stages of mitosis: (PPMAT)
the chromosomes , migrate to the center of the cell, become condensed, centriole formation starts.
the nuclear membrane disintegrates
the chromosomes line up in the equatorial plane (middle) of the cell
chromosomes migrate towards the opposite poles of the cell
- Telophase chromosomes have reached opposite sides of the cell & cell wall constricts to separate the cells in two.
Cyclins are a diverse family of proteins whose defining feature is that they bind and activate some member of the Cdk (cyclin-dependent kinase) family. Although originally identified as enzymes that control cell-cycle events, members of the Cdk family are involved in other cellular processes.
Together the binding of cyclins to their specific Cdk are responsible for leading the eukaryotic cell into the various phases of the cell cycle.
Typically there are 3 main groups of cyclins and Cdks:
- G1 cyclins
- S-phase cyclins
- M-phase cyclins
This is the quality control of the cell cycle. These are points in the cell cycle where the quality of genetic replication is checked. If there are any problems in DNA quality (e.g. mutations) or spindle quality or the presence of Okazaki fragments (these are discontinuous segments of newly formed DNA during DNA replication) the cell is not permitted to proceed in the cell cycle until all of these have disappeared.
All these checkpoints require the services of a complex of proteins. Mutations in the genes encoding some of these have been associated with cancer; that is, they are oncogenes.
Genes encoding the regulatory proteins include p53, ATM (ataxia telangiectasia mutated), MAD (mitotic arrest defective).
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