p53, Genomes, and Teflon

1) A bit of background -- p53 is an extremely famous protein that's primarily responsible for preventing cancer via a variety of mechanisms involving detecting DNA damage, repairing DNA damage, and killing the cell if there's too much DNA damage. Given p53's importance in preventing cancer, it's not surprising that p53 is mutated in more than half of cancers -- breaking p53 makes cancer much more likely to happen. So I got this hairbrained idea for preventing (some incidents of) cancer -- basically, put in a backup copy of p53 that's repressed by transcription of the primary copy (for instance, by putting a nuclease-null cas9 gRNA targeted to the backup p53 inside an intron in the primary). If anything stops the primary from being made, the backup switches on, probably along with a marker of some sort telling you that something's gone wrong with the primary.

...except today I learned that most p53 mutations are point mutations, not frameshifts or big deletions or regulatory knockdown like I expected. In fact, something like 3/4 of p53 mutations are *gain of function* mutations, not knockouts at all! So much for that. (If you have Nature Cell Biology accesssee http://www.nature.com/ncb/journal/v15/n1/full/ncb2641.html for more.)

2) Question: How many species' genomes do you have to sequence to detect conservation of a single nucleotide, assuming realistic mutaiton rates and about a 1% error rate? What about an 8 nucleotide conserved region (as in a transcription factor binding site)? What about a 50 bp exon? Think about this for a minute and see what number you come up with.

The answers, according to Harvard professor (and, more impressively to me, former HHMI Investigator), are about 28 genomes, 4 genomes, and 2 genomes, respectively. See http://tinyurl.com/nvnu2e6 (open access!) for details.

3)  Teflon (polytetrafluoroethylene) is damned tough stuff. Among other things, it can "safely" contain dioxygen difluoride. To quote HyperLuminal from chemistry.stackexchange.com: "Known as the gas of Lucifer,[...] It ignites stuff at temperatures that most of the stuff that we breathe in would be in liquid form. No one really knows about its atomic structure (obviously)." Yet Teflon can hold it just fine. Go teflon.