Double minute chromosomes

Kaufman RJ, Brown PC, Schimke RT. Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. Proc Natl AcadSci USA 1979 76 5669-5673. 

Vitek, J.A. (1987) Similarity in dynamics of single and double minute chromosomes incidence and number of chromosomal aberrations during long-term treatment of a human cell line with methotrexate. Neoplasma 34, 6 665-670. 

Amplification of genes under selective conditions has been widely observed-for example, in development of pesticide-resistant forms of insects. Such amplified structures could arise either through recombination with unequal sister-chromatid exchange, schematized in Figure 25.41, or by a conservative transposition process. Later, homologous recombination within an amplified region can lead to excision of sequences containing one or more amplified sequences. In order to replicate autonomously, these excised sequences must have a centromere. Such elements probably represent the double-minute chromosomes. 

With respect to the damage, the dose rate (i.e. the time during which a certain dose is transmitted to the body) is of great importance. This is illustrated by the following example A low-LET dose of 3 Gy produces 3000 single-strand breaks and 100 double-strand breaks in every cell of a human body. If this dose is transmitted within a short time of several minutes, the damage in the cells cannot be repaired and may result in death. However, if the same dose is spread over a period of about a week, only aberrations in the chromosomes are observed. 

E. coli can divide every 40 minutes. Thus, its DNA (MW = 2.2x 10 ) can be duplicated in 40 minutes (or less). Calculate (a) the number of internucleotide bonds made per minute, (b) the rate of chromosome duplication in terms of mm/min and /xm/min (assuming only one growing point), and (c) the rate at which the double helix unwinds (turns/min) during duplication. 

Fig. 14. Stable unipolar malorientation of two interlocked bivalents in a living grasshopper Melanoplus differentialis) spermatocyte. The kinetochoric ends of the two bivalents are labeled "a,b" and c,d/ respectively, and the time in minutes is indicated on each print. The interlocking was produced by micromanipulation already completed by the 0-minute print the chromosome configuration produced is most readily seen on the 137-and 155-minute prints. Double nondisjunction occurred in anaphase (175 to 289-minute prints). XI,000. (From Henderson and Koch. 1970. Chromosoma, 29 207-216. Modified by omission of four prints.)...

The best known example of an alkaloid which inhibits ceU division in plants is colchicine. Added in minute amounts, this alkaloid interferes with the formation of the cell carokinetic spindle instead of a division of the cell into two daughter cells, a restitutive cell is formed with a doubled set of chromosomes. The alkaloid, while very active on cells of most species of plants, produces no effects in Colchicum autumnale, the most common source of this compound. Alkaloids of Senecio and Crotalaria can cause chromosome breakage in a number of organisms, mostly animals, but are... 

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