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We are grateful to the @snsf.ch for the generous support to this project, and to @embo.org and Novartis Foundation for their direct support to Daniel’s work in our lab. Thanks also to the Functional Genomic Center Zurich for excellent technical support.

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This was truly a joint effort with Ana Losada, Daniel Giménez-Llorente and Ana Cuadrado at @cniostopcancer.bsky.social, providing essential expertise in 3D genome organization. More help from Melani Rodrigues and Moses Aouami in our lab, and Javier Munoz and Ohri Barroso-Gomila at IIS Biobizkaia.

This work largely reflects the creativity, technical skills & impressive resilience of Daniel González-Acosta @daniga90.bsky.social, outstanding postdoc in our lab, currently transitioning towards independence. Dani is a rising star in our field and clearly deserves the largest credit for this work

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Mechanistically, our work supports the emerging role of 3D genome organization in genome maintenance and a novel view of the replication stress response that goes beyond local responses to stress and lesions, instead integrating throughout the nucleus via nuclear architecture and organization.

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Such fork tethering enables coordinated slowdown of DNA synthesis by preventing PRIMPOL engagement and driving fork reversal. While protecting the genome from replication stress, this may support cancer cell resistance to genotoxic treatments and be targeted or defective in cohesin-mutated tumours.

Combining a new MicroC-based method to map 3D-genome interactions at replicating DNA with genetic tools to inactivate cohesin functions, we show that cohesin accumulates at stressed replication forks and uses loop extrusion to modulate 3D interactions among sister forks and neighboring replicons.

Cohesin reshapes replication fork contacts to aid fork slowing and reversal - Nature

Thrilled to share a new important study from the lab, published today in @nature.com, showing how cohesin mediates efficient replication fork plasticity and stress response, using its loop extrusion activity to promote 3D contacts on replicating DNA: www.nature.com/articles/s41...

nature.com

Cohesin-mediated loop extrusion limits sister-fork coupling and tethers nearby replication forks under replication stress, promoting fork reversal and slowing fork progression to safeguard genome...

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This work was brilliantly led in our lab by Cyril Doerdelmann, assisted by Tristan Gasparetto. Eric CW So's group (Tsz Fung Kan and Larissa Bomfim) made key contributions, and together we are now building on these molecular mechanisms to develop new therapeutic strategies for AML

Thus, unlike in solid tumors, PARPi sensitivity in AML appears directly linked to replication fork remodeling, while PRIMPOL-mediated repriming promotes PARPi resistance—likely reflecting exceptionally efficient repair of the resulting ssDNA gaps.

PRIMPOL deregulation, both in vitro and in vivo, can drastically alter AML responses to PARPi and standard-of-care treatments, opening promising therapeutic opportunities for treatment-resistant AML.

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Strikingly, the exquisite PARPi sensitivity of certain AML lines stems from deregulated RECQ1-mediated restart of reversed forks, causing fork acceleration and breakage. By contrast, MLL-rearranged AMLs escape this cytotoxicity through extensive PRIMPOL-mediated repriming.

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Lopes_Lab @lopeslab.bsky.social · 10/07/2026

What if the much-debated mechanisms of PARP inhibitors vary greatly across tissues and tumor subtypes? Our new preprint reveals surprising links between replication fork dynamics and PARPi sensitivity across acute myeloid leukemia (AML) subtypes. www.biorxiv.org/cgi/content/...

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This work was superbly lead by @janakrietsch.bsky.social - senior scientist in our lab - with key contributions from @cejkalab.bsky.social, @smolka-lab.bsky.social, @polosophie.bsky.social and the Sartori lab at IMCR. Curious to hear any feedback on it, while we finalize this work for publication!

Lopes_Lab @lopeslab.bsky.social · 10/07/2026

Thrilled to share a new preprint from the lab, showing that active fork slowing and reversal is not confined to the damaged subnuclear compartment but rapidly extends throughout the nucleus, via non-canonical ATR signaling and modulation of MRN exonuclease activity. www.biorxiv.org/cgi/content/...

biorxiv.org

Non-canonical ATR signalling via NBS1 phosphorylation propagates fork slowing from stressed to unperturbed nuclear regions

DNA replication forks frequently encounter obstacles and remodel into four-way junctions to actively slow DNA fork progression. Fork slowing can also spread to undamaged forks via an ATR-dependent mec...

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Lopes_Lab @lopeslab.bsky.social · 08/06/2026

Don't miss the next GiiN seminars tomorrow (June 9th). Just click here at 17.00h CET 👇 uzh.zoom.us/j/6598481621...

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Lopes_Lab @lopeslab.bsky.social · 17/04/2026

Here is the full 2026/27 program of @genomeiinetwork.bsky.social virtual seminars, chaired by myself and @dimiccolab.bsky.social. Scan the QR code to receive alerts and automated calendar. Don't miss a bunch of exciting talks from established and emerging leaders in genome integrity world-wide!

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Lopes_Lab @lopeslab.bsky.social · 01/04/2026

Another great opportunity for genome integrity / replication stress aficionados to attend two excellent seminars with a simple click. Join us in a few days (Tue April 7th)! 👇

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Lopes_Lab @lopeslab.bsky.social · 26/02/2026

Two more upcoming GIIN virtual seminars you should not miss! Just connect to the Zoom link below on March 3rd, 5pm, CET 👇

Lopes_Lab @lopeslab.bsky.social · 02/02/2026

Tomorrow (Tue 3rd)! PLEASE NOTE THE ALTERNATIVE ZOOM LINK! 👇

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Lopes_Lab @lopeslab.bsky.social · 29/01/2026

Don't miss the opportunity to attend exciting virtual talks from leading scientists in genome integrity, provided by the @genomeiinetwork.bsky.social! Next one is in a few days 👇

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Lopes_Lab @lopeslab.bsky.social · 17/01/2026

Happy to have contributed to this interesting story. Cool experimental system and thought-provoking findings 👍

Lopes_Lab @lopeslab.bsky.social · 08/01/2026

One more upcoming appointment with great science via the Genome Integrity Italian Network (GiiN). Don't miss it, just join via the link 👇

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Lopes_Lab @lopeslab.bsky.social · 19/12/2025

We link replication fork plasticity to another important player of nuclear architecture, i.e. Lamin A/C, by showing that its nucleoplasmic fraction modulates heterochromatic marks and ADP ribosylation levels at replication factories, thereby controlling RECQ1-dependent restart of reversed forks!