Nucleic acid structure & function 2: sequence terms, modifications, mutations, chromatin, etc.

Basics of sequence terminology, base modifications, mutations, translation, chromatin structure, etc.
Part 1: • DNA & RNA structure pa...
blog form: bit.ly/nucleica...
See a DNA double helix, put your right thumb up. If the twist follows your fingers your graphic designer is in luck! The first thing I do when I see a graphic of DNA is give it a thumbs up. Not just because I’m happy to see it (though it is *groovy*) but because I’m checking to make sure it’s RIGHT-HANDED! In order to complement the base pairing we’ll discuss more in a second, the strands adopt a right-handed helical form (to see that it’s right handed, give a thumbs up w/right hand - the direction your fingers are curling is direction DNA curls) 
 
The most common double helix in DNA is “B-form” It has 2 grooves - a larger major groove, & narrower minor groove. These grooves can act like windows for other molecules to “read” their sequence without having to unzip them. RNA can also form double helixes (though usually a more compact “A-form”) & it also forms a variety of structures w/in single strands  
 
In the MAJOR groove you can distinguish all 4 base pairs, but in the MINOR groove you can only tell GC or CG vs AT or TA. I still remember the mnemonic I came up with when taking molecular bio in undergrad… AHA! ADAM ATe A TAMADA! (see pic) 
 
Thanks to DNA’s grooviness, you can read the DNA without disrupting the helix, but if you want to make a copy, you have to open up that region of the helix (MELT it) (don’t worry - it will ANNEAL back together afterwards). It’s easier to pull the strands apart in regions that have lots of A-T pairs because each of those base pairs only has 2 hydrogen bonds versus the 3 of G-C pairs, so regions that have to be opened often are often A-T rich. In cells, proteins called HELICASES help with the separation, but in the lab we can literally melt the strands by heating them up 
 
But the helix is not where the structure stops! - your DNA packs up tight w/help of HISTONES because we have so much DNA it’d never fit in our cells if it weren’t all coiled up (if you stretched it out it would be ~2m (~6.5ft) long) To help it coil & stay coiled ➿ it wraps around “hair rollers” (proteins called HISTONES) to form NUCLEOSOMES, which are like beads on string ➰ 
 
This saves space (& prevents things you don’t want read from being read), but when you do want a region read &/or transcribed, that region must be “opened up.” It’s kinda like when you open a mobile version of a website & it has all the different sections collapsed to save room ▶️ & you have to click on them to expand them if you want to actually read them 🔽 
 
Much of EPIGENETICS involves special proteins adding modifications to the DNA or its “curlers” that help the sections expand if you want to read them 🔽 & collapse if you don’t want them read 🔼. These modifications are often put on histones by post-translationally modifying lysine amino acids in the tails of the histone proteins, as we talked about here: bit.ly/lysinean...
 
How do you know what’s worth reading when? Other proteins are able to read “section headers” - recognize specific DNA sequence motifs (like words) that are present in front of functionally-related genes so that, instead of reading gene-specific headers, it’s more like reading “key words” or indexing terms, so a DNA-binding protein can search for 1 search term & get “hits” on multiple regions or genes which it can act on “simultaneously” - this allows for coordinated activation or deactivation of related genes  
    
more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 bit.ly/2OllAB0 or search blog: thebumblingbioc...