Feels like this paper on protein-templated DNA synthesis by a natural enzyme warrants some comment.
So here's a 🧵. /1
www.science.org/doi/10.1126/...

The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona The kinetochore fibrous corona docks on CENP-E and a second elusive receptor identified as the checkpoint protein BUB1.

The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona | Science Advances www.science.org/doi/10.1126/...

Congratulations @vcmentowski.bsky.social for solving a remarkably challenging molecular puzzle

Thanks to all the authors for their hard work! This work was done by @mpi-nat.bsky.social . We thank ‪@compbiophys.bsky.social and Urlaub laboratory for their help, and @dfg.de and @maxplanck.de for funding. Check it out for many more surprises!
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Feedforward auto-activation: activated ATG101 subsequently quickly activates non-activated ATG101 molecules to create a positive feedforward reaction and supports the local fast assembly of a key complex in autophagy initiation.
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Memory of activation: hysteresis causes ATG101 to ‘remember’ its activation for many hours after dephosphorylation due to the very slow, but spontaneous back-conversion to the default fold.
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Auto-activation: this work proposes an unusual regulatory mechanism where UKL1 kinase initiates an ATG101 auto activation cascade. ULK1 kinase activity dramatically accelerates an extremely slow assembly upon aiding a change in the fold of ATG101.
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In this manuscript, we revisit the question “how is autophagy initiated at the right place and time?”. What started as a relatively straightforward search for the rate-limiting regulatory step, resulted in the discovery of a unique mechanism of regulated protein metamorphosis.
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Influence of ULK1 activity on the memory of ATG101 auto-activation dynamics The initiation of autophagy is marked by the prompt convergence of initiation proteins to form super molecular complexes in spatially-defined autophagic hubs. The recruitment and activation of the ULK...

This was a wild ride!

www.biorxiv.org/content/10.1...

see thread below 🧵👇
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Influence of ULK1 activity on the memory of ATG101 auto-activation dynamics www.biorxiv.org/content/10.1101/2025.06....