Жасушалардағы кішкентай ядролар және геномдық тұрақсыздық

Small nucleus in the cells of some organisms

A micronucleus is a small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal instability. Micronuclei are commonly seen in cancerous cells and may indicate genomic damage events that can increase the risk of developmental or degenerative diseases. Micronuclei form during anaphase from lagging acentric chromosomes or chromatid fragments caused by incorrectly repaired or unrepaired DNA breaks or by nondisjunction of chromosomes. This improper segregation of chromosomes may result from hypomethylation of repeat sequences present in pericentromeric DNA, irregularities in kinetochore proteins or their assembly, a dysfunctional spindle apparatus, or flawed anaphase checkpoint genes. Micronuclei can contribute to genome instability by promoting a catastrophic mutational event called chromothripsis. Many micronucleus assays have been developed to test for the presence of these structures and determine their frequency in cells exposed to certain chemicals or subjected to stressful conditions. The term micronucleus may also refer to the smaller nucleus in ciliate protozoans, such as the Paramecium. In mitosis it divides by fission, and in conjugation a pair of gamete micronuclei undergo reciprocal fusion to form a zygote nucleus, which gives rise to the macronuclei and micronuclei of the individuals of the next cycle of fission.

The micronucleus tests provide important information about a chemical's ability to interfere with chromosome structure and function. For instance, many known human carcinogens test positive in mammalian micronucleus tests. In these tests, organisms are treated with a chemical and the resulting frequency of micronucleated cells is measured. If there is a marked increase in the number of cells with micronuclei, it can be concluded that the chemical induces structural and/or numerical chromosomal damage. Since micronucleus tests must be performed on actively dividing cells, bone marrow stem cells and the erythrocytes they produce through cell divisions are ideal candidates. These cells experience constant, rapid turnover and the lack of a true nucleus in erythrocytes makes micronuclei easily visible under a microscope. Sex chromosomes contribute to the majority of chromosome loss events with increasing age. In females, the X chromosome can account for up to 72% of the observed micronuclei of which 37% appear to be lacking a functional kinetochore assembly possibly due to X chromosome inactivation. Multiple studies have shown that the frequencies of autosome positive micronuclei in both genders and of sex chromosome positive MN in men were similar and remained unchanged in older groups while the frequency of X positive MN in women was higher than the average frequency of autosome positive MN and continued to increase until the oldest age. In normal people and many other mammals, which do not have nuclei in their red blood cells, the micronuclei are removed rapidly by the spleen. Hence high frequencies of micronuclei in human peripheral blood indicate a ruptured or absent spleen. In mice, these are not removed, which is the basis for the in vivo micronucleus test.