A report on Epigenetics and Carcinogenesis

Cancers and tumors are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.

DNA associates with histone proteins to form chromatin.

The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis

Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors.

Some acetylations and some methylations of lysines (symbol K) are activation signals for transcription when present on a nucleosome, as shown in the top figure. Some methylations on lysines or arginine (R) are repression signals for transcription when present on a nucleosome, as shown in the bottom figure. Nucleosomes consist of four pairs of histone proteins in a tightly assembled core region plus up to 30% of each histone remaining in a loosely organized tail (only one tail of each pair is shown). DNA is wrapped around the histone core proteins in chromatin. The lysines (K) are designated with a number showing their position as, for instance (K4), indicating lysine as the 4th amino acid from the amino (N) end of the tail in the histone protein. Methylations [Me], and acetylations [Ac] are common post-translational modifications on the lysines of the histone tails.

Tissue can be organized in a continuous spectrum from normal to cancer.

Many tumor suppressor genes effect signal transduction pathways that regulate apoptosis, also known as "programmed cell death".

The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division.

- Carcinogenesis

Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, DNA methylation reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning.

- Epigenetics

2 related topics with Alpha

DNA damage resulting in multiple broken chromosomes

DNA repair

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Collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome.

Structure of the base-excision repair enzyme uracil-DNA glycosylase excising a hydrolytically-produced uracil residue from DNA. The uracil residue is shown in yellow.

Double-strand break repair pathway models

DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide ester bond between the phosphate backbone and the deoxyribose nucleotides.

DNA repair rate is an important determinant of cell pathology

Most life span influencing genes affect the rate of DNA damage

A chart of common DNA damaging agents, examples of lesions they cause in DNA, and pathways used to repair these lesions. Also shown are many of the genes in these pathways, an indication of which genes are epigenetically regulated to have reduced (or increased) expression in various cancers. It also shows genes in the error-prone microhomology-mediated end joining pathway with increased expression in various cancers.

However, it has become apparent that cancer is also driven byepigenetic alterations.

Epigenetic repression of DNA repair genes in accurate DNA repair pathways appear to be central to carcinogenesis.

Evolution

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Change in the heritable characteristics of biological populations over successive generations.

In 1842, Charles Darwin penned his first sketch of On the Origin of Species.

DNA structure. Bases are in the centre, surrounded by phosphate–sugar chains in a double helix.

This diagram illustrates the twofold cost of sex. If each individual were to contribute to the same number of offspring (two), (a) the sexual population remains the same size each generation, where the (b) Asexual reproduction population doubles in size each generation.

Mutation followed by natural selection results in a population with darker colouration.

Simulation of genetic drift of 20 unlinked alleles in populations of 10 (top) and 100 (bottom). Drift to fixation is more rapid in the smaller population.

Homologous bones in the limbs of tetrapods. The bones of these animals have the same basic structure, but have been adapted for specific uses.

A baleen whale skeleton. Letters a and b label flipper bones, which were adapted from front leg bones, while c indicates vestigial leg bones, both suggesting an adaptation from land to sea.

Common garter snake (Thamnophis sirtalis sirtalis) has evolved resistance to the defensive substance tetrodotoxin in its amphibian prey.

Geographical isolation of finches on the Galápagos Islands produced over a dozen new species.

Tyrannosaurus rex. Non-avian dinosaurs died out in the Cretaceous–Paleogene extinction event at the end of the Cretaceous period.

The hominoids are descendants of a common ancestor.

As evolution became widely accepted in the 1870s, caricatures of Charles Darwin with an ape or monkey body symbolised evolution.

Since the beginning of the 21st century and in light of discoveries made in recent decades, some biologists have argued for an extended evolutionary synthesis, which would account for the effects of non-genetic inheritance modes, such as epigenetics, parental effects, ecological inheritance and cultural inheritance, and evolvability.

If cells ignore these signals and multiply inappropriately, their uncontrolled growth causes cancer.