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Emilio Lecona's Lab

@ubisystemlab.bsky.social

Account of the Chromatin, Cancer, and Ubiquitin System Lab at the CBM. We study DNA replication dynamics, ubiquitin and SUMO signaling, and their roles in cancer. Now on Bluesky!

Posts Replies Media

Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

Huge thanks to all people involved, @smoa-cbm.bsky.social and flow cytometry facilities from @cniostopcancer.bsky.social and @cbm-csic-uam.bsky.social.

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Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

So, to sum up: VCP/p97 ➡️ POLA/PRIM on chromatin ➡️ priming ➡️ basal RSR activation! This work was led by @emlecona.bsky.social from @cbm-csic-uam.bsky.social in collaboration with Juan Mendez' group from @cniostopcancer.bsky.social. Want to dive a little bit more in our work? Click here! rdcu.be/eu1yo

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Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

And the activation of the RSR induced by VCPi is relevant, as the phosphorylation of CHK1 leads to an arrest in G2/M. More importantly, CHK1 activation is lost when we block the priming action of POLA/PRIM.

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Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

What are the consequences of more POLA/PRIM on chromatin? We observed that the inhibition of VCP/p97 also increased priming by POLA/PRIM, as observed in the EdU comet assay.

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Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

In fact, we showed that VCP/p97 and POLA/PRIM do interact. Interestingly, VCP/p97 inhibition could not induce the accumulation of POLA/PRIM on chromatin if origin firing is inhibited with CDC7i.

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Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

It struck our attention that the increased activation of the RSR induced when VCP/p97 is inhibited is mirrored by the accumulation of POLA/PRIM on chromatin. Could our two guests be working together?

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Emilio Lecona's Lab @ubisystemlab.bsky.social · 29/07/2025

First, we found that VCP/p97 is necessary for DNA replication and its inhibition leads to defects in fork progression and origin firing that result in the activation of the RSR.

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