Why DNA is like a phone cable (Recap of a Talk by Prof. Jacqueline Barton)

[Computer rendering of DNA. Via Caroline Davis2010 on Flickr & CC 2.0] 

The Talk:

“DNA-mediated Signaling with Metalloproteins”

In Plain English:

DNA can conduct electricity–like metal wire–and that helps the cell life

The Speaker:

Jacqueline Barton of Caltech

The Sponsor:

MIT Inorganic Chemistry (invited by the grad students)

What It Covered:

When Jacqueline Barton’s lab began publishing papers claiming that DNA can conduct electricity, many of her colleagues didn’t believe them. But in experiment after experiment, they kept finding that they could send small amounts of electricity–much lower than the amount that flows through your charger cord–from an electrode on one end of a DNA strand through to the other.

The exceptions were stretches of DNA with “missense mutations“, hiccups in the genetic code that violated the rule of “G” aligns with “C” and “A” aligns with “T”.

A,T, G, and C are biologists’ shorthand for four small molecular structures– adenine, thymine, guanine, and cytosine– that repeat over and over again along DNA’s backbone. It just so happens that a G-C pair takes up exactly the same amount of space and adds exactly the same amount of twist as an A-T pair.  Anything else–a misplaced guanine, a broken cytosine, or a chemical tag on thymine– throws the DNA’s twist out of whack. And apparently,  the missense mutations also blocked electrical currents’ flow through a tiny gap in the center of the DNA.  Mismatched base pairs or base pairs that were even slightly damaged blocked the electrons’ path.

Metal wires can carry far larger amounts of electricity than DNA, but very few wires as thin as DNA can carry an electrical current as far. Barton thinks it can’t be a coincidence that the molecule our cells use to store genetic info is also an effective long-distance (over the micron-scale) electrical wire, so her lab’s focus has become studying the behavior of electrical pulses through DNA and how various molecules affect those electrical transmissions. 

They’ve found quite a lot of them. Today, Barton is one of the most decorated chemists in the world. She received a National Medal of Science in 2011 and is only the third woman ever to receive the American Chemical Society’s highest honor–the Priestley Medal.

Her talk at MIT was whirlwind overview of some of her lab’s greatest hits from the last decade or so.

Barton says that many of the molecules that take advantage of DNA’s electricity-carrying power are proteins that repair broken base pairs. They’re kind of like a telephone repairman, she says (in an analogy that she hopes the young ‘uns in the audience still understand). Telephone repairmen aren’t looking for the telephone cables that do send a signal; they’re looking for ones where the signal has failed to get though. Similarly, the DNA-repairing proteins detect mutation points by sending electrons up and down the DNA strand. The electrons peel off of iron clumps within the protein and travel through the inner reaches of the DNA tunnel. The proteins spot problem areas in the DNA by zeroing in on sections in the DNA where the electric signal has stopped.  “It’s not a great wire, because it’s a bettor sensor than a wire,” Barton said. 

There are several different varieties of these DNA-repairing proteins. (Bacteria, for instance, use a different set than we mammals do.) Two of the proteins Barton mentioned have adorably Star-Wars-character-like nicknames: Endo (short for “Endonuclease III”) and DinG (pronounced “din-GEE”). 

My Personal Take:

When I was scanning through upcoming talks, this lecture immediately caught my eye because it’s billed as an inorganic chemistry seminar (“inorganic” = about molecules that don’t have carbon in chemistry-speak), but the first word in the title is DNA.

DNA has carbon. Lots and lots of carbons.  It’s unambiguously organic.

I scrolled to her name, which conjured hazy memories of reading something by journalist Natalie Angier that involved a large DNA model, a Caltech chemist’s office, and lots of hand gestures. Being a science writer means reading articles about scientists, DNA, and hand-waving basically every day; my memory for scientists I’ve met or interviewed via phone is pretty good, but it’s impossible to remember every one I read about. If something about Barton stuck from just an article, I figured I should go. 

[Angier, by the way, wrote a book that undergrad “aspiring science writer” Diana absolutely adored called The Canon. In some ways I’ve grown out of it; the intro that once seemed relevatory now seems over-the-top.  But Chapters 1, 2, & 3 are absolutely essential reading for anyone who’s training to be a science writer.] 

Since Barton’s talk was one where the graduate students were allowed to choose who to invite, I shouldn’t have been so surprised that they chose someone in biochemistry/biophysics.  Word on the street in Cambridge-Bubble Territory* is that chemists and physicists are flocking into biology, formerly regarded as a squishy scientific realm without interesting problems. Gene expression, proteomics, and systems biology have all presented new challenges that appeal to programmers, physicists, and people who can actually spend a whole workday focusing on chemistry glyphs.

On level, it’s exciting. On another level, it’s frightening. Chemistry, physics, and math have always been tough for me personally, and all of those fields are dominated by men. (Biology is too, but traditionally to a slightly less severe degree.) When I realized that I could actually walk into MIT Biochemistry and Bioengineering lectures on proteins I’d never heard of and still follow, I felt like I’d discovered a hidden talent. Now I often feel obligated to use it. Partly because well glycosylation, transcription factors, bioelectric gradients, and DNA folding all come up often enough that at least a handful of people in the science press corps should be able to write about them, but also because I think it’s important for the incoming generation of biophysics and biochem journalists to be women.  

But selling stories on those intricate and esoteric topics can be tough.

Hearing women who’ve not only been telling these stories but also leading the original research in the field is enormously helpful. And Barton is an enthusiastic and engaging speaker.

Although I do share her concern that someday there’ll be a generation of chemistry grad students who won’t recognize the telephone wire analogy.

*(“Cambridge Bubble” = the area around Harvard and MIT where it’s possible for almost all of your nearby friends and acquaintances to be grad students, lab techs, programmers, and/or start-up employees. It can sometimes lull us into forgetting that the most of the country is actually half Republican, that more people go to community college than to 4-year schools, and that most people would have to stop for a minute and think before remembering what a “protein” means in the context of proteins flying around interacting with DNA.)

Best One-Liner:

Barton: [displaying an HHMI movie of proteins making copies of DNA]

[Video via Howard Hughes Medical Institute & JSSBio97 on Youtube

Barton: “I want to get at something very specific here: This is really complicated. Things are coming and going all the time!”

Biggest Misconception to Avoid:

Barton spent a lot of her talks focusing on metalloproteins–proteins that have at least one metal ion somewhere in their structure–but it’s important to note that metalloproteins aren’t rare at all.  Since metal ions are great for coercing chemicals to trade electrons around, they can be very handy for proteins that actually want to get something done.

 

Tl:DR:
Some proteins can send zappy little jolts of electricity from one end of a DNA strand to another. Cells use this ability to help repair-proteins spot broken or mutated spots in the DNA.

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