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If you’re looking for a holiday gift for the ambitious learner in your life, go to Brilliant.org/SciShow to learn more about their gift subscriptions. [♪ INTRO] Tweezers are probably one of the most useful tools in your bathroom medicine cabinet. They can pluck hairs from your eyebrows, pull splinters from your foot, or tighten the screws in your glasses.

And by using some tricks of physics, a very special type of tweezers can even unzip DNA. The ability to isolate a single strand of DNA is incredibly useful, because it could help us with DNA sequencing, studying how genes are expressed, understanding how DNA is repaired, and just give us a better idea of cellular mechanics in general. But the process of isolating a DNA strand had stumped scientists for years.

Not just because DNA is tiny, but because it’s usually wound up in packages that are super hard to detangle. Most of the time, DNA doesn’t look like the nice, loose double-helix you might see in a biology textbook, and the chromosomes it makes up don’t usually look like those cute little X’s. Those X-shaped chromosomes can be conveniently dragged around when the cell is dividing, but the rest of the time, it makes more sense for DNA to be packaged in a more usable form.

Stretched end to end, most cells have over 2 meters of DNA. You’ve got to organize it somehow. So in the cell, the DNA double helix is normally wrapped around proteins called histones.

It’s almost like wrapping up a yo-yo, except in this case, there are hundreds of yo-yos on a single string. The string winds itself around a yo-yo for a few turns, then starts winding up the next yo-yo. At the end, you're left with a pile of yo-yos with all the string tucked away.

Each of these yo-yos is also bound to an additional type of histone called a linker histone to form a complex called a chromatosome. Each chromatosome plus the stretch of DNA linking it to the next one forms a nucleosome. An entire chromosome’s worth of DNA ends up in nucleosomes clustered together in a highly-ordered structure of yo-yos called chromatin.

Being wrapped up like this keeps DNA compact, organized, and protected. But it also means that if you want to separate a single strand, you don’t just have to unzip it from its partner strand. You also have to unwind it from the histones and pull it from the mass of nucleosomes.

In other words, imagine that you’re trying to unravel a single thread from the string in a pile of yo-yos. And let’s throw some jacks and pick-up sticks into the pile too, since there are other proteins in chromatin that a DNA strand can also get stuck on. But in 1986, scientists figured out a way to grab and hold onto particles as small as 25 nanometers using what they dubbed optical tweezers.

Optical tweezers rely on a force scientists have known about since the early 1600s, called radiation pressure. The idea is that photons of light actually apply a tiny amount of physical pressure to objects that they hit. But it’s such a tiny amount of pressure that it usually doesn’t do anything, because basically every object light hits is too big to react to such a little push.

But when the laser was invented in the 1960s, scientists finally had a beam of light that they could use to move things. Lasers were able to focus on a small enough point, and hit particles with a small enough mass, that the photons could actually move them. With a little bit of quantum mechanical know-how, it’s possible to manipulate the light so that it pulls, rather than pushes.

Which means that scientists can actually use a laser to gently pull on a strand of DNA, separating it from its partner strand and attached histones. Finally being able to remove single strands of DNA from a nucleosome has taught scientists a lot about the structure of these complexes. For one thing, we’ve learned about the strength and stability of DNA-histone binding.

In a 2021 study, researchers in Israel discovered that when those extra linker histones bind with DNA that’s already wrapped up around a yo-yo, the histone-DNA bonds within the yo-yo tighten up. In other words, the linker histone that forms a chromatosome actually makes the base structure more stable. It also turns out that the segments of DNA wrapped up in a single nucleosome are about 40% longer than we originally thought.

But optical tweezers haven’t just taught us about the structures DNA is packaged in. They’ve taught us more about DNA itself, too. Like, as DNA goes through its life cycle, it gets twisted, untwisted, pulled apart, squashed down, wrapped up, and stretched out.

DNA is the cell’s library, and that’s no way to treat a book. By using optical tweezers to pull on and stretch out DNA, scientists have been able to learn more about how elastic DNA is, and measure the amount of mechanical force it can withstand. And they’ve been able to measure the way that enzymes unwind and copy DNA strands as the cell copies its DNA in preparation to divide.

Experiments with optical tweezers have shown that copying DNA happens in short bursts, with pauses in between when the enzyme and DNA strand temporarily separate from each other. And how quickly the enzyme moves during those bursts of activity is dependent on how much tension is in the DNA strand. Now, this may all seem like a bunch of very tiny details to be learning with the coolest tweezers ever.

But a better understanding of the basic structure and processes of DNA is super important to understand what’s going on when something goes wrong. So all this basic information has implications for understanding the role of chromatin in diseases, and hopefully eventually better treatments. After all, once you start pulling on a thread, who knows what mysteries you’ll unravel.

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