Recombination instability

Whiteway, M. S. and A, Ahmed, "Recombinational Instability of Chimeric Plasmid in Saccharomyces cerevisiae, " Molecular Cellular Biology (January 1984) 195 - 198. 

In order to sustain the ON state by double injection or by tunneling it is necessary, as Lucas (1971) points out, that the carrier lifetime is longer than the transit time. Her model of switching is based on the idea that beyond a critical injection current both electron and hole traps are neutralized and as a consequence recombination is sharply decreased and the diffusion length becomes of the order of the film thickness. This sharply increases the bulk conductance and the sustaining field is again concentrated at the electrodes as in Figure 6.21(c). Lucas obtains for the critical current density at which the so-called recombination instability occurs... 

The helicases are enzymes central to life itself. The nature of double-stranded DNA means that before a polymerase can begin to copy the appropriate region of the nucleic acid, the two strands have to be unwound the separation of the two strands is the function of the helicase (Fig. 2). An indication of the significance of this family of enzymes is seen in the so-called Werner syndrome, where the helicase function required in the suppression of inappropriate recombination events is defective and causes genomic instability and cancer (for a review see Cobb and Bjergbaek 2006). 

Fukuoka was found to be homozygous for the 1615 G to A (539 Asp to Asn) mutation. This mutation occurred at relatively conserved amino acid residues and caused an alteration in hydrophobicity. Recently, we examined the structure-function relationship of these variants using the recombinant protein (F14). Although all of the four variants were found to be heat labile, the residual GPI activity seems to reflect clinical severity, such as the degree of anemia and episodes of hemolytic crisis. GPI Matsumoto, associated with severe anemia and hemolytic crisis, was extremely unstable, and GPI Iwate, which is associated with compensated hemolytic anemia, showed moderate heat instability. Affinity for substrate, fructose-6-phosphate, was slightly decreased in GPI Narita and GPI Fukuoka, which were associated with moderate anemia and hemolytic crisis. 

It should be noted that the unfolding kinetics can sometimes involve quite complex unfolding schemes of different substates in equilibrium with the native state. Staphylococcal nuclease is an example of such behavior, known to unfold with three different substates that exhibit an equilibrium that does not appear to shift with temperature.49 Irreversible aggregation processes of proteins have been known to involve first- or second-order reactions.132141 The mechanism of recombinant human interferon-y aggregation is an example where thermodynamic and kinetic aspects of the reaction provided a powerful tool for understanding the pathway of instability and permitted a rationale for screening excipients that inhibited the process.141... 

Plasmid instability can arise when the foreign protein is toxic to the host cell. During rapid growth plasmids may be lost or the copy number reduced, allowing the non-recombinant cells to take over. As a... 

The hallmark and molecular characteristic of progression is karyotype instability. This is due to disruption of mitotic apparatus, alteration of telomere function, DNA hypomethylation, chromosome translocations and recombination, gene amplification, and gene transposition. There is also alteration of mismatch repair genes in some cancers. 

Fig. 3.2(a). Its typical value varies between 3-5 ao for metals [3, 4] and nearest neighbours for alkali halides. In some semiconductors, e.g., In2Te3, the radius of the instability zone could be very large (e.g., [19-22]). The relevant physical mechanism is annihilation of interstitial atoms with their own vacancies, which occurs in the time interval of several lattice vibrations, 10-13 s, and results in the restored perfect crystalline lattice. This mechanism takes place for all kinds of solids. Thus we can write down phenomenologicaly for the recombination probability (per unit time)... 

Tunnelling recombination of primary F, H pairs can result either in closely spaced v+,i pairs (the so-called a, I centres) which annihilate immediately due to Coulomb interaction and a consequently large instability radius. However some i ions occur in crowdion configurations, and leave vacancy moving away up to 4-5 ao even at 4 K [31]. The distinctive feature of tunnelling recombination is its temperature independence, which makes it one of the major low-temperature secondary processes in insulating solids with defects. 

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