In all, 17 of the mutations disrupted the loop 2 or loop 3 domains of TP53 protein.
TP53 mutations disrupting the loop 2 and loop 3 domains of the protein have been shown to predict poor survival in breast cancer (Borresen et al, 1995) and colorectal cancer (Borresen-Dale et al, 1998).
Moreover, simultaneous knockdown of MAF1 with either Pol III or BRF1 (a subunit of TFIIIB) disrupted the looping formation.
The authors state that 'Moreover, simultaneous knockdown of MAF1 with either Pol III or BRF1 (subunit of TFIIIB) disrupted the looping formation.
Background/Purpose: Recently, the authors have shown that in human fetuses suffering from gastroschisis, there is an amniotic fluid inflammatory response and that amniotic fluid exchange designed to disrupt the inflammatory loop seems to have a favorable impact on outcome.
ADT involves administering luteinizing-hormone-releasing hormone agonists or antagonists to disrupt the feedback loop within the hypothalamic gonadal axis, suppressing testosterone production by the testes.
However, unlike treatments that disrupt the telomere loop, T-oligos do not cause digestion of the 3' telomere overhang (repeats of TTAGGG sequences) or otherwise alter endogenous chromosomes [ 10].
It was postulated previously that the mechanism of doxorubicin-induced SIPS depends on both functional p53 and telomere dysfunction rather than shortening, but such dysfunction can disrupt the telomere loop structure (Elmore et al. 2002).
To further substantiate our hypothesis that T-oligo treatment mimics physiological exposure of the 3' telomere overhang following telomere loop disruption [ 9- 13, 15, 17] 17], we introduced TRF2DN [ 20] into MCF-7 cells, a manipulation known to disrupt the telomere loop and to lead to exposure and digestion of the 3' overhang [ 15, 17, 20].
Thus perturbation by phase advancing or slowing of one (or more) element(s) through tremor frequency matched stimulation can disrupt the recurrent loop, perhaps as presynaptic spiking activity now falls in refractory periods of postsynaptic neural activity, and diminish tremor amplitude.
