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I am still puzzled by the claim that these additional RT stops arise from common base oxidation products, such as 8-oxoG or 5'-HOC.
First, the authors assume these "extra" stops arise from non-scissile base damage, but of course, they could arise from strand scission events.
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The elusive nature of malignancy initiations, and its progression until a threshold, above which it becomes problematic to stop, arises from the fact that it depends upon conditions that occur intermittently.
In order to filter out the short stops that arise, e.g. during commutes, we consider only stops with duration greater than 15 minutes.
In the highly conserved and purine-rich terminal SRL loop, multiple stop sites arise in RNA isolated from cells treated with increasing cisplatin concentrations.
This means they can resolve issues much quicker and in some cases stop them arising altogether.
Non-stop mRNAs can arise naturally through premature termination or polyadenylation within ORFs, which are estimated to occur for up to 10% of all transcriptional events (Frischmeyer et al., 2002).
In addition, such non-stop mRNAs could also arise due to mutations, readthrough of stop codons due to PSI+ that limits the translation termination factor function (Wilson et al. 2005), or endonuclease cleavage sites with the open reading frame.
You have to trust that there is more snow beyond what your headlight can illuminate, have enough confidence in yourself to know that you can handle any terrain in front of you, and be cautious enough that you can quickly turn or stop should an obstacle arise.
Furthermore, we do not understand how stop codon variants first arise within populations, leading to changes in gene models over evolutionary time.
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