Congrats Martijn, well deserved!

Congrats, very exciting work!

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

Mutational signature catalogue (MUSIC) of DNA double-strand break repair Genome alterations arise from inaccurate DNA repair, accumulating into distinct mutational signatures. Here, we investigate the role of every genomically encoded gene in double-strand break (DSB) repa...

Very exciting work by the Tijsterman lab www.biorxiv.org/content/10.1...

A must for all DNA repair aficionados!

Egmond DNA Repair Meeting → April 19–24, 2026 🇳🇱
✔️ Confirmed top speakers
✔️ Ample opportunities for talks & posters

Don’t miss it: dnarepairmeeting-egmond2026.com

@puckknipscheer.bsky.social, @luijsterburglab.bsky.social, @marcelvanvugt.bsky.social, @sylvie-noordermeer.bsky.social, @titiasixma.bsky.social, @marcelvanvugt.bsky.social, @marteijnlab.bsky.social

CIP2A is required for mitotic recruitment of the SLX1/XPF/MUS81 tri-nuclease complex to replication stress-induced DNA lesions to maintain genome integrity Perturbed DNA replication can lead to incompletely replicated DNA when cells enter mitosis and can interfere with chromosome segregation. Cells therefore require mechanisms to resolve these lesions du...

Extremely happy to share that my main PhD project about CIP2A-TOPBP1 and the SMX complex is now available online as pre-print.

Huge thanks to all co-authors but especially @marcelvanvugt.bsky.social for giving me the opportunity to work on this exciting project!

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

REV7 functions with REV3 as a checkpoint protein delaying mitotic entry until DNA replication is completed How cells ensure that they enter mitosis after completing replication of their genome is not fully resolved. Sobkowiak et al. describe a checkpoint involving REV7. This checkpoint has mechanistic similarities to the spindle anaphase checkpoint mediated by…

REV7 functions with REV3 as a checkpoint protein delaying mitotic entry until DNA replication is completed

A CPC-shelterin-BTR axis regulates mitotic telomere deprotection - Nature Communications Here the authors reveal how telomeres signal mitotic stress. A key protein network alters their structure exposing telomere ends to signal mitotic stress, ultimately triggering a controlled DNA damage...

1/Out today in @naturecomms.bsky.social,

“A CPC-shelterin-BTR axis regulates mitotic telomere deprotection”.

Here we identify the mechanism that unwinds telomere-loops (t-loops) during mitotic arrest to activate the DNA damage response and signal mitotic stress.

www.nature.com/articles/s41....

WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2 Inhibitors of the protein kinase WEE1 have emerged as promising agents for cancer therapy. In this study, we uncover synergistic interactions between WEE1 small-molecule inhibitors and defects in mRNA translation, mediated by activation of the integrated stress response (ISR) through the kinase GCN2. Using a pooled CRISPRi screen, we identify GSPT1 and ALKBH8 as factors whose depletion confer hypersensitivity to the WEE1 inhibitor, AZD1775. We demonstrate that this synergy depends on ISR activation, which is induced by the off-target activity of WEE1 inhibitors. Furthermore, PROTAC-based WEE1 inhibitors and molecular glues show reduced or no ISR activation, suggesting potential strategies to minimise off-target toxicity. Our findings reveal that certain WEE1 inhibitors elicit dual toxicity via ISR activation and genotoxic stress, with ISR activation being independent of WEE1 itself or cell-cycle status. This dual mechanism highlights opportunities for combination therapies, such as pairing WEE1 inhibitors with agents targeting the mRNA translation machinery. This study also underscores the need for more precise WEE1 targeting strategies to mitigate off-target effects, with implications for optimising the therapeutic potential of WEE1 inhibitors. ### Competing Interest Statement The authors have declared no competing interest.

in parallel, a study that describes very similar results was posted by the lab of Stephen Jackson from Cambridge UK:
www.biorxiv.org/content/10.1...

Thanks to the many collaborators; the labs of Thijn Brummelkamp, Alexander van Oudenaarden, Steven de Jong, Frank Sicheri, Marvin Tanenbaum @marvintanenbaum.bsky.social @jervdberg.bsky.social @rinskjetjeerdsma.bsky.social @mauritsroorda.bsky.social @daaninthelab.bsky.social

WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response The WEE1 kinase negatively regulates CDK1/2 to control DNA replication and mitotic entry. Genetic factors that determine sensitivity to WEE1 inhibitors (WEE1i) are largely unknown. A genome-wide inser...

Happy to post a new study on BioRxiv, where we show Integrated Stress Response activation as an off-target effect of multiple clinically evaluated WEE1 inhibitors. Team effort with the lab of Dan Durocher @durocher1.bsky.social and many others. www.biorxiv.org/content/10.1...

Congrats Agnel, very exciting work!

Very nice work! Congrats

The transcriptomic architecture of common cancers reflects synthetic lethal interactions - Nature Genetics Tumor cells upregulate compensatory buffering genes following tumor suppressor loss. These genes may represent new synthetic lethal partners that could be harnessed therapeutically.

We show transcriptomic buffering of tumour suppressor loss via syn. lethal genes is not anecdotal but a cancer hallmark. Buffering also seen in BRCAness, predicts penetrant syn leth effects and outcome. @icr.ac.uk @cancerresearchuk.org @breastcancernow.bsky.social www.nature.com/articles/s41...

SAVE THE DATE! The next EMBO | EMBL Symposium on 'DNA replication and genome maintenance: from basic biology to disease' will be held October 20-23, 2026.
 
Organized by Helle Ulrich (IMB), Johannes Walter (Harvard) and Anja Groth (Danish Cancer Institute).

www.embl.org/about/info/c...

Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions Schmid and Walter train a classifier that discerns functionally relevant structure predictions in proteome-wide protein-protein interaction (PPI) screens using AlphaFold-Multimer, and they use this co...

Nice resource! #AlphaFold #PPI #ProteinInteractions

Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions: Molecular Cell www.cell.com/molecular-ce...

Professorship in genetics and molecular cell biology (W3) (f/m/d) - Academic Positions The University of Cologne is one of the oldest and largest universities in Germany. With its six Faculties covering a broad spectrum of disciplines and its i...

*Tenured full Professorship in Genetics and Molecular Cell Biology* at the University Of Cologne, Germany

It's an opportunity to rebuild the place that used to be home to luminaries including Benno Müller-Hill, Max Delbruck, Campos-Ortega, Diethard Tautz Maria Leptin, Thomas Langer

Spatial mapping of DNA synthesis reveals dynamics and geometry of human replication nanostructures DNA replication is essential to life and ensures the accurate transmission of genetic information, which is significantly disturbed during cancer development and chemotherapy. While DNA replication is...

Beautiful work by the Lemmens lab! www.biorxiv.org/content/10.1...

Mitotic transcription ensures ecDNA inheritance through chromosomal tethering Extrachromosomal DNA (ecDNA) are circular DNA bodies that play critical roles in tumor progression and treatment resistance by amplifying oncogenes across a wide range of cancer types. ecDNA lack cent...

exciting work: RNA-mediated tethering of DNA during mitosis www.biorxiv.org/content/10.1...

Great work!

6 Postdoctoral and PhD positions in Center for Epigenetic Cell Memory (EpiC) The Center for Epigenetic Cell Memory (EpiC) is a new Center of Excellence that will be established based on funding by the Danish National Research Foundation.

🚨𝐌𝐚𝐣𝐨𝐫 𝐉𝐨𝐛 𝐀𝐥𝐞𝐫𝐭!🚨The Groth @groth-anja.bsky.social, Mailand, Nilsson @nilssonlab.bsky.social & Krietenstein @nilskrietenstein.bsky.social labs are hiring 𝟔 𝐏𝐡𝐃&𝐩𝐨𝐬𝐭𝐝𝐨𝐜𝐬 to join the new Center for Epigenetic Cell Memory (EpiC) in Copenhagen, Denmark. Apply here: tinyurl.com/yvd93na2 & please share!

Dear all,

Postdoc positions are available to work on (1) the role of DNA strand break repair proteins during DNA replication and (2) the molecular/structural biology of XRCC1 protein complexes, as part of our work on genetic diseases & cancer. Contact me if interested: k.w.caldecott@sussex.ac.uk

Excited to present Social DNAing tomorrow. I’ll talk about our work led by @szmyd-radoslaw.bsky.social in collaboration with @radoncdocgee.bsky.social.

12 pm Eastern USA

Thanks Shan Zha for the invite.

www.cancer.columbia.edu/research/pro...

First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer - Nature Cancer Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are effica...

🌟Check out new online content: study from Daniel Dauch's lab:
doi.org/10.1038/s430...

I am curious!

ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage - Nature Structural & Molecular Biology In this study, the authors show that DNA-damage-mediated transcriptional stress induces NF-κB through IRAK1, allowing damaged cells with impaired transcription to initiate an inflammatory response wit...

Today @naturesmb.bsky.social 🥳, we report that the activation of NF-κB after DNA damage can occur through two distinct mechanisms. While ATM triggers NF-κB activation after DSBs, we found that IRAK1 specifically induces NF-κB in response to DNA damage causing transcriptional stress.

Mark your calendar: the next Egmond DNA repair meeting will take place in 2026 from April 19 - 24!

You can pre-register to receive announcement here: forms.lumc.nl/lumc2/Egmond

Registration will open by June 2025/

Congrats!!

Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing DNA and protecting genome integrity, forms filamen...

NEW in @science.org, so happy to contribute to our understanding of the molecular machine, Fidgetin-like 1 (FIGNL1), and elucidating the mechanism of why cells cannot survive when it is lost! #ScienceResearch science.org/doi/10.1126/... (1/7)