The West Lab @ The Crick

And that’s a wrap! 🎉
Our first conference of 2026 is complete, and what a fantastic way to start the year!
We hope to see both familiar and new faces at the next #DRRSC meeting in 2028.
Click here to Sign up for updates on the conference series: bit.ly/4bceiZb

To kickstart this new Bluesky account: We're hiring!
The Bertolin Lab @dundee.ac.uk is looking for a postdoc to work on DNA-end homeostasis & genome stability, funded by Wellcome Trust Award. Exciting science, fantastic environment, founding role in the lab.
Details in the flyer — get in touch! 👇

Cohesin guides homology search during DNA repair using loops and sister chromatid linkages Accurate repair of DNA double-strand breaks (DSBs) is essential for genome stability, and defective repair underlies diseases such as cancer. Homologous recombination uses an intact homologous sequenc...

I am happy to share that my postdoctoral work in the @gerlichlab.bsky.social at @imbavienna.bsky.social is finally out 🎉!
Our study reveals how cohesin guides focused and accurate homology search.
Read more 👉 www.science.org/doi/10.1126/...
Follow along for key insights and updates! 🧵

Cohesin drives chromatin scanning during the RAD51-mediated homology search Cohesin folds genomes into chromatin loops, the roles of which are under debate. We found that double-strand breaks (DSBs) induce de novo formation of chromatin loops in human cells, with the loop bas...

Thrilled to share that my postdoc research is published today in @science.org! We found that DNA repair uses cohesin complexes to build new chromatin loops that guide the homology search and boost accurate repair! 1/n
www.science.org/doi/10.1126/...

A role for human senataxin in contending with pausing and backtracking during transcript elongation Senataxin (SETX) regulates RNA polymerase II (RNAPII) transcription and helps maintain genome stability, at least partly by suppressing R-loops. Howev…

I’m very happy to share Zhong Han’s beautiful work on the biochemical function of Senataxin, encoded by a gene that is mutated in rare and early-disabling neurodegenerative diseases. Turns out it rescues backtracked RNA polymerase II during early transcription! www.sciencedirect.com/science/arti...

Cryo–electron microscopy visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2 Homologous recombination repairs DNA double strand breaks and protects stalled replication forks, but how the five RAD51 paralogs contribute to these processes remains unclear. Mutations in the RAD51 ...

In summary:

➡️ RAD51B complex promotes RAD51 filament assembly on RPA coated DNA
➡️ XRCC3 complex caps filaments & promotes homologous pairing

📄 science.org/doi/10.1126/science.aea1546

Thanks to our collaborators in @boultonlab.bsky.social group also at @crick.ac.uk (8/8)

Additionally, XRCC3 complex capped filaments promote D-loop formation — a key HR intermediate for repairing DSBs and stalled forks.

This shows that capping by the XRCC3 complex directly enhances RAD51’s synaptic activity. (7/8)

XRCC3 remodels the terminal RAD51 N-terminal domain to bind in trans.

This rearrangement is conserved in archaeal paralog RadB and yeast paralog complex Rad55–Rad57, revealing a deeply conserved filament-capping mechanism. (6/8)

Using cryo-EM, single-molecule and biochemical assays ❄️💡, we found these two tetramers functionally differ:

➡️ The RAD51B complex assembles RAD51 filaments in an ATP hydrolysis–coupled, dynamic manner.
➡️ The XRCC3 complex caps the 5′ ends of RAD51 filaments – independent of ATP hydrolysis (5/8)

It is known that the five RAD51 paralogs exist as a tetramer (RAD51B-C-D-XRCC2) and dimer (RAD51C-XRCC3). Our data overturn this paradigm:

➡️ The ‘dimer’ actually exists in a tetrameric XRCC3 complex: XRCC3-RAD51C-RAD51D-XRCC2.
➡️ Therefore, there are two near-identical tetrameric assemblies.

Structure and function of the RAD51B–RAD51C–RAD51D–XRCC2 tumour suppressor - Nature Structural and biochemical studies of the RAD51B–RAD51C–RAD51D–XRCC2 complex reveal that it uses coupled RAD51B and RAD51C ATPase activities to promote the nucleation and extension of RAD51 ...

In our previous work, we described the structure-function relationship of the RAD51B-RAD51C-RAD51D-XRCC2 complex (www.nature.com/articles/s41...) in the assembly of RAD51 filaments on RPA-coated ssDNA, which marks double-strand break resected DNA. (3/8)

Homologous recombination repairs DNA double-strand breaks via the RAD51 filament, which searches for homology and drives strand exchange. BRCA2 and the RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) promote filament assembly; however, their mutation causes cancer and Fanconi anaemia. (2/8)

‼️ Excited to share our new paper out now in @science.org ‼️

We describe a new tetrameric RAD51 paralog complex – XRCC3-RAD51C-RAD51D-XRCC2 – which caps the end of RAD51 filaments.

Link: www.science.org/doi/epdf/10....

Thread ⬇️ (1/8)

From serendipity to strategy: molecular glue degraders in cancer therapeutics Targeted protein degradation is an elegant therapeutic strategy that harnesses the cell’s own degradation machinery to selectively eliminate target proteins. This approach marks a paradigm shift in...

New review out on molecular glues: turning serendipitous hits into smartly designed drugs that tag cancer-linked proteins for destruction 🧬💥💊
www.tandfonline.com/doi/full/10....

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 photo from the recombination mechanisms conference in Crete last week. Thanks to the @fusionconf.bsky.social team, speakers, poster presenters and attendees for a great meeting!

Update on #Recombination25 Conference! 🚨
📅RD & PS Deadline: 13th March 2025. DON'T MISS OUT!
🌟Grants are available for students, postdocs & junior investigators!🌟
For more details, visit bit.ly/41v8IuK or email Felicity at 📧felicity@fusion-conferences.com
@westlabcrick.bsky.social

Talk submission deadline coming up on 10th February 2025!

The West lab @crick.ac.uk has finally joined bluesky! Looking forward to sharing (and discovering!) new work 🧬 #recombination #dnarepair #BRCA #cryoEM #cellbiology