Peter Ly

USP1/UAF1 targets polyubiquitinated PCNA with an exo-cleavage mechanism that can temporarily enrich for monoubiquitinated PCNA - Nature Communications DNA damage tolerance is regulated by ubiquitination of PCNA. Here, the authors present kinetic and structural studies showing that USP1/UAF1 prefers trimming K63- and K48-ubiquitin chains down over cl...

I'm very proud that our paper, and with that the main project of my PhD, has just been published by @natcomms.nature.com! 🎉
Here, we reveal the unique, molecular mechanism by which USP1/UAF1 cleaves ubiquitin chains on PCNA, which may direct DNA damage tolerance.

doi.org/10.1038/s414...

S-phase checkpoint protects from aberrant replication fork processing and degradation Abstract. Replication stress, a hallmark of cancer cells, is detected by checkpoint mechanisms that trigger a range of cellular responses. Among these, the

Excited to share my first PhD paper published in @narjournal.bsky.social! This project was led by amazing supervisor Belén Gómez González in @aguilerloop.bsky.social lab. Thanks to all colaborators of Blanco and Diffley teams. I hope you like it!
Now online here 👇🏼 academic.oup.com/nar/article/...

Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers Nature Communications - The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the...

With super Roman Chabanon and Sophie Postal Vinay, we show that inhibition of RNA editor ADAR1 causes a new form of BRCA synthetic lethality>autocrine inferferon poisoning. Relevant for ADAR1 drug discovery. Could provide a mechanistically different approach than PARPi. rdcu.be/eyo6t

FEN1 is critical for rapid single-strand break repair in G1 phase Abstract. Flap endonuclease 1 (FEN1)-dependent long-patch repair has been considered a minor sub-pathway of DNA single-strand break repair (SSBR), activate

Our latest study is out in Nucleic Acids Research. FEN1 is critical for rapid single-strand break repair in G1 phase url: academic.oup.com/nar/article/...

The discovery of CENP-A, the centromere-specific histone H3 variant turns 40 years!
Grant Rowley wrote a wonderful historical piece on the cell cycle control of this fascinating piece of chromatin! Check it out.
link.springer.com/article/10.1...

Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique...

New preprint! We solve a mystery you didn't know existed. Mitotic cells lack new transcription but require ongoing translation. Interphase mRNA half life is only 2-4 hrs. So how do cells arrest in mitosis for hours without depleting their transcriptomes?

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

Congrats Abby – your lab is on a roll!

The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate - Nature Cell Biology Marin et al. report the role of lamin proteins and the lamin B receptor (LBR) in chromatin positioning at the nuclear periphery. Knockout of all lamins and LBR in mouse embryonic stem cells leads to h...

Another paper bluetorial! Today: how does the spatial location of genes influence their function? (1/n) www.nature.com/articles/s41...

Lamin B1 and LAP2β resist cytoskeletal force to maintain lamin A/C meshwork organization and preserve nuclear integrity | Molecular Biology of the Cell The nuclear lamins are extremely long-lived proteins in most cell types. As a consequence, lamin function cannot be effectively dissected with temporal precision using standard knock-down approaches. ...

The nuclear lamina strengthens the nucleus and organizes the genome. So what happens when you acutely degrade it in living cells? Not what we thought! (1/n)
www.molbiolcell.org/doi/10.1091/...

Calyculin A Induces Premature Chromosome Condensation and Chromatin Compaction in G1-Phase HeLa Cells without Histone H1 Phosphorylation https://www.biorxiv.org/content/10.1101/2025.07.16.665228v1

Nanoscale 3D DNA tracing in non-denatured cells resolves the Cohesin-dependent loop architecture of the genome in situ - Nature Communications A nanoscale 3D DNA tracing workflow visualizes Cohesin-dependent loops in single, structurally well-preserved cells. Computer simulations based on the tracing data give further insight into how Cohesi...

Our new non-denaturing nanoscale 3D DNA tracing technology provides single-cell (and sister-chromatid specific!) readout of chromatin structure with 10kb genomic resolution - Check it out!

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

Congratulations to Kai and Oyvind!!

CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS Abstract. Disassembly of the replication machinery (replisome) from chromatin is an active process driven by two ubiquitin ligases Cul2LRR1 and TRAIP, whic

It is finally out 👍😀. Great job of the team (mostly absent from Bsky) and @m-saponaro.bsky.social

CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS url: academic.oup.com/nar/article/...

Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization Telomerase ribonucleoprotein (RNP) synthesizes telomeric repeats at chromosome ends using a telomerase reverse transcriptase (TERT) and a telomerase RNA (hTR in humans). Previous structural work showe...

Proud to share our work where we resolved a longstanding question regarding the existence of a human telomerase dimer and provided insights into its function. Led by 3 amazing lab members in collaboration with @yiliangding.bsky.social and @rdaslab.bsky.social.
www.science.org/doi/10.1126/...

Our new preprint is out! We revisit the associations between p53 status and cancer aneuploidy using TCGA data. Here’s a breakdown of our findings. Important work spearheaded by the talented PhD candidate Joana Marques. Check it out here: www.biorxiv.org/content/10.1...
(1/8)🧵

Cell enlargement causes mitotic errors and aneuploidy in cells that evade senescence after CDK4/6 inhibition CDK4/6 inhibitors (CDK4/6i) arrest the cell cycle in G1 leading to cellular overgrowth and p53-dependent senescence. They are used to treat metastatic HR+/HER2- breast cancer, but resistance is common...

Delighted to share our latest work showing how cells that evade #senescence after CDK4/6 inhibition are primed to become aneuploid because of their increased size (due to defects in cohesion and the mitotic checkpoint). Great work by fab PhD student Aanchal Pareri 👏🧪

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

The adaptive molecular landscape of reprogrammed telomeric sequences Telomeric sequences vary across the tree of life and intimately co-evolve with telomere-binding protein complexes. However, the molecular mechanisms allowing organisms to adapt to new telomeric sequen...

Superhappy to share the last paper from my PhD in @litinice.bsky.social lab. We evolved yeasts with humanized telomeric repeats and discovered that they adapt through amplification of telomere-binding proteins and inactivation of the DNA damage response.

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

Wishing farewell to the first member of our lab, Qing Hu, as she embarks on a new adventure in the Laboratory Genetics and Genomics fellowship program at UCLA. Good luck Qing!

New preprint from Kelsey Fryer in the lab using ChAR-seq to identify RNAs that are bound to human centromeres. Lots of surprises! #centromere #RNA www.biorxiv.org/content/10.1...

Postdoc positions open in my lab (Francis Crick Institute) to study

1. initiation of DNA replication.

2. chromatin replication/epigenetic inheritance.

Great for biochemists, biophysicists and cryo-EM/cryo-tomography scientists.

Deadline 3 August 2025.

crick.wd3.myworkdayjobs.com/External/job...

A checklist for designing and improving the visualization of scientific data Nature Cell Biology - Creating clear and engaging scientific figures is crucial to communicate complex data. In this Comment, I condense principles from design, visual perception and data...

I gave in! After students asking for it, I now made a simple figure design checklist.
To help all scientists w/o graphic skills create clear, accessible, and truthful charts!
-> Out in @nature Cell Biology: rdcu.be/erwl4

#DataVisualization #PhD #SciComm

Thx for review @bethcimini.bsky.social + 2

RNA transcripts regulate G-quadruplex landscapes through G-loop formation G-quadruplexes (G4s) are prevalent DNA structures that regulate transcription but also threaten genome stability. How G4 dynamics are controlled remains poorly understood. Here, we report that RNA tra...

Excited our paper is out! G-quadruplex (G4) unwinding via an intricate G-loop assembly and disassembly mechanism maintains genome integrity. Pioneered by Koichi Sato with great collaborators Jing Lyu and @simonelsasser.bsky.social Check it out: www.science.org/doi/10.1126/science.adr0493 🧵(1/4)

Genome rearrangements induced by the stimulation of end-joining of DNA double strand breaks through multiple phosphorylation of MRE11 by the kinase PKB/AKT1 Abstract. Genetic instability is a major hazard threatening the fate of cells and ultimately of organisms. DNA double-strand break (DSB) is a highly toxic

The hyper-activation of DNA double-strand break repair by the AKT1/PKB oncogene generates genetic instability.
(A new role for the oncogene AKT1: the phosphorylation of MRE11).
academic.oup.com/nar/article-...

Unraveling mitochondrial influence on mammalian pluripotency via enforced mitophagy Enforced mitophagy enables efficient mitochondrial depletion in pluripotent stem cells and embryos, allowing the creation of human-ape fusion PSCs with defined mitochondrial origins, which reveal crit...

Excited to share our new study in Cell—congrats to Daniel, co-authors, and our collaborators in the @peterlylab.bsky.social What began as pure curiosity led to a tool for modulating mitochondrial abundance in vitro and in vivo. A new direction for the Wu lab begins! www.cell.com/cell/fulltex...

Just out: BRCA2 reversion mutation–independent resistance to PARP inhibition through impaired DNA prereplication complex function | PNAS www.pnas.org/doi/10.1073/... @mskcancercenter.bsky.social @kyriepappas.bsky.social #SawyersLabMSKCC

Illustration of two people, one holding a large pencil, the other walking along a path of diverging arrows. Hedline is "Rules all PIs should follow."

#NextGenSci asked young scientists to write a rule that all principal investigators should be required to follow to improve the experience of young scientists in their lab.

Check out their answers on #NationalHigherEducationDay: scim.ag/45zsFEr

👋 Are you looking for a postdoc position? Do you think microtubules are fascinating? Then we might have the job for you! 2-year funded postdoc to join our lab!
👉 deadline 20/06
👇 check it out

www.godinholab.com

Centromeric DNA amplification triggered by viral proteins activates nuclear cGAS Herpesvirus proteins disrupt centromeres, triggering centromeric DNA amplification and local nuclear activation of the nucleic acid sensor cGAS. This reveals an immune surveillance mechanism in the nu...

Thrilled to share our latest @cp-cell.bsky.social.
We present VICAR (VIral-induced Centromeric DNA Amplification and Recognition), a new defense system to detect viruses in the nucleus based on nuclear cGAS.
www.cell.com/cell/abstrac...

🧬 New from crystal structures from our lab in EMBO Journal! We reveal how the FANCM enzyme, an emerging therapeutic target it cancer, has evolved to specifically recognise branched DNA and activate the Fanconi anaemia pathway of DNA repair. doi.org/10.1038/s443... 🧵👇

Postdoctoral Research Associate in the Blackford Group A position as Postdoctoral Research Associate is available at the Department of Cellular and Molecular Medicine, in the group headed by Dr. Andrew Blackford. Th

We’re #hiring, please share! A fully funded #postdoc position is available in my lab to work on DNA damage response mechanisms.

Please get in touch with your CV if you are interested; closing date: 27th June 2025.

More details here: candidate.hr-manager.net/ApplicationI...

Thrilled to see #SAVANA out in @natmethods.nature.com 🥳 SAVANA detects haplotype-resolved somatic SVs, copy number aberrations & infers tumour purity & ploidy using long-read sequencing with or WITHOUT a matched germline control 👇https://www.nature.com/articles/s41592-025-02708-0