Lopes_Lab

Lopes_Lab

@lopeslab.bsky.social

We use molecular & cell biology and single-molecule approaches to study DNA replication stress and its contribution to genome instability in cancer.

448 followers336 following57 posts

This was truly a joint effort with Ana Losada, Daniel GimΓ©nez-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.

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.

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.

This work largely reflects the creativity, technical skills & impressive resilience of Daniel GonzΓ‘lez-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

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.

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.

View full thread

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

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

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.

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.

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.orgNon-canonical ATR signalling via NBS1 phosphorylation propagates fork slowing from stressed to unperturbed nuclear regionsDNA 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...

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)! πŸ‘‡

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 πŸ‘‡

GIIN@genomeiinetwork.bsky.social

Another great science appointment is coming up with @nitikataneja.bsky.social and @doksanilab.bsky.social! Join us live on Tuesday, February 3rd at 5pm (Rome) / 11am (NYC). Zoom link: uniroma1.zoom.us/j/95149984403 Register here to stay in the loop: docs.google.com/forms/d/e/1F...

TODAY! πŸ‘‡

Lopes_Lab@lopeslab.bsky.social

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

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

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!

TODAY! Don’t miss it! πŸ‘‡

Lopes_Lab@lopeslab.bsky.social

In a few days we'll have our last appointment (for this year) with great virtual talks via the GiiN. Please note in agenda and join us with a click! πŸ‘‡

We will be collecting applications for one more week (Dec 5th), then proceed shortlisting candidates for the next β€œSNSF starting grant” deadline (May 2026). Please hurry up sending your docs and/or spread the news! (…and mind the β€œSwiss link” in the eligibility criteria) πŸ‘‡

Lopes_Lab@lopeslab.bsky.social

New important opportunity for young PI recruitment at our Institute! Please spread the news. Interested candidates should carefully check their eligibility for the indicated SNSF funding schemes, before submitting their application πŸ‘ πŸ‘‡ www.imcr.uzh.ch/dam/jcr:3d1f... www.imcr.uzh.ch/en.html

Happy to have contributed to this interesting study from penengolab.bsky.social! another interesting example of how chromatin modifications and their readers orchestrate replication fork plasticity and protection πŸ‘πŸ‘‡

The EMBO Journal@embojournal.org

H2B ubiquitination by RNF20/40 safeguards replication fork dynamics in human cells, by facilitating fork reversal and recruiting RNF169 that protects from excessive degradation of nascent DNA @penengolab.bsky.social and collaborators www.embopress.org/doi/full/10....

Tomorrow (Tue 9th) at 5 PM CET. Don't miss it!

Lopes_Lab@lopeslab.bsky.social

Mark your calendar (September 9th) for two more exciting virtual seminars of the Genome Integrity Italian Network (GiiN). Full schedule for the Fall season also provided just below. No registration required, just come and join us with a click! πŸ‘‡

Mark your calendar (September 9th) for two more exciting virtual seminars of the Genome Integrity Italian Network (GiiN). Full schedule for the Fall season also provided just below. No registration required, just come and join us with a click! πŸ‘‡

Exciting science ahead! Hope to see many of you online on Tuesday 6th (just connect, no registration needed)

GIIN@genomeiinetwork.bsky.social

The Genome Integrity Webinar Series continues on Tuesday, May 6th at 5PM (Rome) / 11AM (New York) with an exciting discussion on DNA damage response and repair @kajastelab.bsky.social Join via Zoom: uniroma1.zoom.us/j/95149984403

More exciting genome integrity research at the horizon. Register to receive alerts and marks for your calendar πŸ‘πŸ‘‡

GIIN@genomeiinetwork.bsky.social

We thank @martakova.bsky.social and Mate Maus for sharing their research with our community at yesterday's seminar! Our next seminar on Tuesday, May 6th will feature @kajastelab.bsky.social and Raphael Ceccaldi. Subscribe here to receive the reminder: t.co/Hv6iLmjlly

Exciting seminar series from Genome integrity italian Network (GiiN), chaired by myself and Raffaella Di Micco! Short talks (2x30’), at convenient time for EU/USA attendees. Big shots and raising stars in an expanding field. See flyers + link to receive email alerts. Please repost to your network!πŸ‘‡

Exciting seminar series from Genome integrity italian Network (GiiN), chaired by myself and Raffaella Di Micco! Short talks (2x30’), at convenient time for EU/USA attendees. Big shots and raising stars in an expanding field. See flyers + link to receive email alerts. Please repost to your network!πŸ‘‡

Just landed back in the lab, after a few incredible days on the Alps! A wonderful opportunity to consolidate our projects, rethink our strategies, explore new ideas, blend as a team... and, above all, have a lot of fun! Proud of you guys... and certainly much stronger now! πŸ‘πŸ€©

a great conference, and a tribute to a great scientist and man πŸ‘‡

Jihane Basbous@jihanebasbous.bsky.social

Dear Colleagues, We are extending our early bird registration deadline to December 17th as there have been some issues both with the Carte Achat service as well as with the website. All have now been sorted.We look forward to seeing you for this special event that will honour the memory of Angelos.

You are up to date.