Pablo Alcón

A tribute to Pedro Cuatrecasas, the Spaniard who (whilst working in the US) co-invented affinity chromatography.

Structure of telomerase dimer with key catalytic codes and H/ACA RNPs highlighted with schematic illustrating how dimer disruption leads to shortened telomeres and disease mutations of the dimers causes premature ageing diseases

Sebastian Balch, Zala Sekne & Elsa Franco-Echevarría in @kellythd-nguyen.bsky.social's group have confirmed the existence of dimeric telomerase and illustrated how it is key to telomere maintenance:
www2.mrc-lmb.cam.ac.uk/first-struct...

#LMBResearch @yiliangding.bsky.social @rdaslab.bsky.social 🧪

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/...

Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression Zinc finger proteins (ZNFs) are the largest family of transcription factors, yet how they activate gene expression remains unclear. In this study, we identified Zincore, a protein complex consisting o...

In today’s publication in Science we introduce Zincore: a novel protein of QRICH1 and SEPHS1 and functions as a transcriptional coregulator dedicated to zinc finger transcription factors. Here’s how we found it: 🧵 www.science.org/doi/10.1126/... 1/11

Wish I could be there!

An unmissable chance to hear Richard Henderson speak in the magical setting of Fonseca, Salamanca.

❄️⚡🔬

Check out this new review (with animations, natch) of mechanisms of licensing origins of DNA replication - a wonderful (and continuing!) collaboration with Bruce Stillman @cshlnews.bsky.social and John Diffley @crick.ac.uk! www.nature.com/articles/s41...

A picture of a bottle of hummus. It is labeled NATURE HUMMUS

These NPG spinoff journals are out of control

Structural and functional analysis of the Mycobacterium tuberculosis MmpS5L5 efflux pump presages a pathway to increased bedaquiline resistance Bedaquiline, an antitubercular drug that targets ATP-synthase, is a key component of a new oral drug regimen that has revolutionized the treatment of multi drug resistant tuberculosis. Clinical bedaqu...

Bedaquiline resistance driven by the MmpS5L5 efflux pump is threatening the drug regimens used to treat MDR-TB.

In our new preprint, we used structural and genetic approaches to better understand how MmpS5L5 effluxes bedaquiline and how future resistance may evolve. 🧵🔽

#TBsky #MicroSky #TB

Symposium
"The structure and workings of molecular machines”
📍 University of Salamanca, Historic building
📅 Sunday June 29, 2025
⌚Starts 10:00 am
Organized by @usaloficial.bsky.social‬ / @ucciusal.bsky.social‬
With :
@ciccancer.bsky.social‬
@interibfg.bsky.social‬
@cnb-csic.bsky.social‬
LUMES-USAL

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...

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...

Beautiful work. Congrats Koichi, Puck and all involved!

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)

US doctors rewrite DNA of infant with severe genetic disorder in medical first Gene-editing breakthrough has potential to treat array of devastating genetic diseases soon after birth, scientists say

www.theguardian.com/science/2025...

New gene linked to severe cases of Fanconi anemia - News Each of us is, genetically speaking, a bit like a ramshackle house where molecular handymen work 24/7 to fix creaky beams, clogged pipes, and faulty wiring.

Mutations in FANCX appear to cause a lethal form of Fanconi anemia, a finding from the Smogorzewska lab in @jclinical-invest.bsky.social that sheds light on unexplained pregnancy loss and offers new avenues for genetic screening. #RockefellerScience

Happy Europe Day!

We're excited to welcome Shabih Shakeel from @wehi-research.bsky.social for a seminar at @molbiolau.bsky.social on 26 May.

🧬🔬

Join us if you're in the Aarhus area!

Details here:

The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient, DSB-induced open chromatin, where it can be stabilized by co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second distinct function promoting a G2 arrest that is dependent on the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase. ### Competing Interest Statement The authors have declared no competing interest.

Super cool new preprint: FANCD2:FANCI is a sensor of open chromatin, independent of DNA damage, but further increased at double strand breaks.
www.biorxiv.org/content/10.1...

Reducing the effects of radiation damage in cryo-EM using liquid helium temperatures | PNAS The physical limit in determining the atomic structure of biological molecules is radiation damage. In electron cryomicroscopy, there have been num...

After years parked at a Polara, I’m excited to share that my PhD work is finally out! We figured out why imaging at liquid helium temperatures wasn’t working—and how to fix it.
🔗 www.pnas.org/doi/10.1073/...

🥶

A reminder that this week I am in Denmark, talking at Aarhus (tomorrow, Wednesday 23rd) and then Copenhagen (Pioneer Institute/Natural History museum, Thursday 24th). I will be briefly reminding people about @embl.org and then talking about two pieces of research involving Danish data

Kelly Nguyen with her research group

Excellent opportunity available for a motivated #postdoc to join @kellythd-nguyen.bsky.social’s group investigating the roles of histones in regulating telomerase using a multi-disciplinary approach.
More details: www.nature.com/naturecareer...
Apply by 04 MAY
#PostdocJobs #ScienceJobs

Enhorabuena @isanchezlo.bsky.social !

Repost appreciated:

Open #PhDposition in structural virology in my group! Join us in Umeå, 🇸🇪 to uncover how arboviruses remodel the cellular interior. In situ #cryoET combined with #virology, #cellbiology, and #biophysics.

Deadline 4 May. More info: www.carlsonlab.se/join/

Schematic illustrating the structural changes undergone by MukBEF SMC complex during DNA capture and ingestion.

How do SMC complexes capture DNA? 🧪

Led by Frank Bürmann, Jan Löwe’s & Mark Dillingham’s groups have identified the directional loading mechanism the bacterial SMC complex MukBEF uses to capture & ingest DNA, & found a phage inhibitor to this pathway.

Read more: tinyurl.com/4s8nrrkk

#LMBResearch

You look at science (or at least talk of it) as some sort of demoralizing invention of man, something apart from real life, and which must be cautiously guarded and kept separate from everyday existence. But science and everyday life cannot and should not be separated.

Rosalind Franklin (to father)

PAF15-PCNA assembly exhaustion governs lagging strand replication and replisome integrity Genome replication in eukaryotic cells is surveyed by the S-phase checkpoint, which orchestrates sequential replication origin activation to avoid exhaustion of hitherto poorly defined rate-limiting r...

Thrilled to share our lab's first preprint, led by an exceptional PhD student Gita Chhetri and with the support of wonderful collaborators, we find that replisome function is rate-limited by strand-specific PCNA dynamics. Hope you will enjoy reading.

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

Brief teaser:

Great news, congrats! 🍻

Structural mechanism of LINE-1 target-primed reverse transcription Long interspersed element-1 (LINE-1) retrotransposons are the only active autonomous transposable elements in humans. They propagate by reverse transcribing their mRNA into new genomic locations by a ...

Excited to share our latest work, led by the incredible @automnenine.bsky.social (now an Ass. Prof. at Princeton)! We uncover key insights into the retrotransposition mechanisms of LINE-1 ORF2p, the enzyme responsible for writing a significant portion of our genome.
www.science.org/doi/10.1126/...

A drawing of two figures standing behind a DNA double helix. The figure in the rear is reading a scroll titled ‘LINE-1’, whilst the figure in the foreground is pulling apart the DNA double helix to glue in a new, red strand labelled ‘LINE-1’. The foreground figure has ‘ORF2p’ written across the chest and a bottle of paste at its feet.

How does LINE-1 remodel human DNA to insert its sequence throughout the genome?
Led by @automnenine.bsky.social, @kellythd-nguyen.bsky.social's group conducted a structural investigation into the molecular mechanisms behind retrotransposition of LINE-1.
Read more: tinyurl.com/4wunsj5e
#LMBResearch 🧪