New discovery from our #CDlab reported in Cell @cp-cell.bsky.social today: SMC motor proteins have a left-right ‘gearbox’ and can switch direction in DNA loop extrusion! www.sciencedirect.com/science/arti... 1/ - ThreadSky

ceesdekker.bsky.social • 110 days ago

New discovery from our #CDlab reported in Cell @cp-cell.bsky.social today:
SMC motor proteins have a left-right ‘gearbox’ and can switch direction in DNA loop extrusion!

https://www.sciencedirect.com/science/article/pii/S0092867424014338

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lloeff.bsky.social•110 days ago

Congratulations @romanbarth.bsky.social @ceesdekker.bsky.social @gruberlab.bsky.social beautiful work!

ceesdekker.bsky.social•110 days ago

As clear from my enthusiastic tweets before 😉, SMC complexes are molecular motors that make loops into DNA, which are crucial for the structure and regulation of our chromosomes. The field has been puzzling HOW they do so. Measuring the motor properties provides the base for such an understanding
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ceesdekker.bsky.social•110 days ago

A puzzling feature controversy was whether or not SMC proteins are directional: Some (incl us) reported that they reel in DNA from one side only. Other reported symmetric reeling in from both sides. Today we resolve this – as SMCs loop DNA strictly asymmetrically but they switch direction over time!

ceesdekker.bsky.social•110 days ago

We observed this asymmetric DNA loop extrusion for all eukaryotic SMC complexes (cohesin, condensin, Smc5/6), indicating a shared common mechanism.

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ceesdekker.bsky.social•110 days ago

For cohesin we even identified the ‘gear lever’, the protein subunit NIPBL, that sets the direction of loop extrusion.

This was shown from beautiful single-molecule experiments where green-red NIPBL would exchange on the SMC which correlated to direction changes in loop extrusion.

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ceesdekker.bsky.social•110 days ago

This new phenomenon of direction switching (as well as SMC diffusion and slipping that we also observe) helps to better explain chromosomal capture data – indicating that it occurs in our cells.

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ceesdekker.bsky.social•110 days ago

Finally, we suggest that this direction switching of the DNA loop extrusion is caused by DNA strand exchange mediated by NIPBL exchange

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