Such an epigenetic alteration can cause expression of the RNA or protein to no longer respond to an external stimulus.
Receptors are created, or expressed, from instructions in the DNA of the cell, and they can be increased, or upregulated, when the signal is weak, or decreased, or downregulated, when it is strong.
[citation needed] Their level can also be up or down regulated by modulation of systems that degrade receptors when they are no longer required by the cell.
Upregulation of receptors, on the other hand, can result in super-sensitized cells, especially after repeated exposure to an antagonistic drug or prolonged absence of the ligand.
[3] The internalization of the insulin molecules provides a pathway for degradation of the hormone, as well as for regulation of the number of sites that are available for binding on the cell surface.
Family-based, adoption, and twin studies have indicated that there is a strong (50%) heritable component to vulnerability to substance abuse addiction.
[9] Especially among genetically vulnerable individuals, repeated exposure to a drug of abuse in adolescence or adulthood causes addiction by inducing stable downregulation or upregulation in expression of specific genes and microRNAs through epigenetic alterations.
[12][13][verification needed] Investigation of epigenetic down- or upregulation of repaired DNA genes as possibly central to progression of cancer has been regularly undertaken since 2000.
PARP1 and FEN1 are essential genes in the error-prone and mutagenic DNA repair pathway microhomology-mediated end joining.
PARP1 is over-expressed in tyrosine kinase-activated leukemias,[16] in neuroblastoma,[17] in testicular and other germ cell tumors,[18] and in Ewing's sarcoma.