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Reposted by Wei-Ting Lu

JStark lab @jstarklab.bsky.social · 8d

www.nature.com/articles/s41... saw @lablegube.bsky.social present this last week. Provides important clarity on RNA at chromosomal DSBs. Including rigorously debunking the nascent synthesis idea.

Transcriptional repression facilitates RNA:DNA hybrid accumulation at DNA double-strand breaks - Nature Cell Biology

Saur, Lesage et al. report that RNA:DNA hybrids arise at double-strand breaks in transcribed genes, independently of de novo recruitment of RNA polymerase II/III, as a result of DSB-induced transcriptional repression.

www.nature.com

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Reposted by Wei-Ting Lu

Adam Phillippy @aphillippy.bsky.social · 14d

🚂 The T2T train keeps rolling: "The formation and propagation of human Robertsonian chromosomes" with Gerton and Garrison labs is out! What's a Robertsonian chromosome? Let Jen tell you herself in this great video, or read our paper: [1/3]
📺 youtu.be/JmlY5omxQVc
📄 www.nature.com/articles/s41...

How Stowers Scientists Found the DNA Site Where Robertsonian Chromosomes Fuse

YouTube video by Stowers Institute for Medical Research

youtu.be

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Reposted by Wei-Ting Lu

Nature Genetics @natgenet.nature.com · 23d

📢OUT @natgenet.nature.com

📰DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.

By Francisco Gimeno-Valiente, Nnennaya Kanu and colleagues.

⬇️

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

DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution - Nature Genetics

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

www.nature.com

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Reposted by Wei-Ting Lu

Nature Cell Biology @natcellbio.nature.com · Aug 22

💫NEW: @brianstrahl.bsky.social & co report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity.
👉https://rdcu.be/eBW3D
bit.ly/3Vff6DO

A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability - Nature Cell Biology

Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associat...

bit.ly

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Wei-Ting Lu @weitinglu.bsky.social · Aug 19

I am delighted to announce that I am starting my lab next month in @oncology.ox.ac.uk @ox.ac.uk It is such a privilege to be a part of this storied institution!
Also, we are hiring - if chromosomal instability and cancer biology excite you, come join the fun!
Job Specification: lnkd.in/e8-3hyfr

This link will take you to a page that’s not on LinkedIn

lnkd.in

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Reposted by Wei-Ting Lu

Eileen Parkes @eileenparkes.bsky.social · May 12

Using snRNA-sequencing (Izar lab @columbiauniversity.bsky.social) with matched multiplex immunophenotypic profiling (@jleslie1.bsky.social) we found tumor cell-intrinsic innate immune activation and intratumoral myeloid infiltration as phenotypic consequences of ongoing micronucleation in EAC. 7/11

Image shows cell types which correlate with increasing chromosomal instability (myeloid populations dominate) and representative images of inflamed, CINhigh tumor and a CINlow tumor

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Reposted by Wei-Ting Lu

Cancer Research UK @cancerresearchuk.org · Apr 27

Wei-ting Lu presents data from the TRACERx lung cancer study on FAT1 alterations and chromosomal instability.

#AACR2025 | @weitinglu.bsky.social | @crick.ac.uk

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Reposted by Wei-Ting Lu

Esashi Lab @esashilab.bsky.social · Feb 25

We are delighted to share our latest work, characterising the role of BRCA2 and its binding partner PALB2 at centromeres, just out in the latest issue of Cell Reports. ⬇️

www.cell.com/cell-reports...

The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability

Graham et al. demonstrate that BRCA2 and PALB2 protect centromere integrity in non-cancerous cells through distinct mechanisms, partly counteracting the mismatch repair factor MLH1. In cancer cells, B...

www.cell.com

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Wei-Ting Lu @weitinglu.bsky.social · Jan 30

I got an idea to make you feel *worse* 🙃🙃-- read Michael Lewis's the fifth risk.

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Wei-Ting Lu @weitinglu.bsky.social · Jan 17

We are fortunate to get a trial of the NL5+ confocal system from confocal.nl which is a total gamechanger. @crick.ac.uk @calm-stp.bsky.social just got a NL5+ system after the trial -- can't wait to have more fun with it♥️!! 4/4

Homepage - Confocal NL - Designed to respect your cells

Discover the confocal systems that enable you to perform deep and fast live cell imaging, beyond the diffraction limit using only nanowatts of laser power.

confocal.nl

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Wei-Ting Lu @weitinglu.bsky.social · Jan 17

The biggest nemesis of live microscopy is light toxicity. The success rate for mitotic imaging is painfully low because one has to balance resolution vs cell death – either you have a blurry movie or a high-resolution movie showing a dead cell. 3/4

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Wei-Ting Lu @weitinglu.bsky.social · Jan 17

The cover is designed by Jeroen at Phsopho Animation,
who converted a mitotis time-lapse movie into some awesome cover art. One can see that chromosomes (white) align and then pulled apart by tubulin (red) as the cell divides, showing lagging chromosomes and chromosomal bridges. 2/4

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Wei-Ting Lu @weitinglu.bsky.social · Jan 17

We’re thrilled to see our research has been highlighted as the cover of NCB this month 🎉 🎉. We are honoured to share this issue with thought-provoking articles investigating multiple aspects of chromosomal instability and mitosis @dfachinetti.bsky.social
@thecesarelab.bsky.social 🧵 1/4

Nature Cell Biology @natcellbio.nature.com · Jan 17

👋🏿Happy new year and our first 2025 issue's out!
Cover: #chromosomal instability in #cancer

👉Review on #TranscriptionFactors and #cell quiescence
🔬#heterochromatin #embryo #DNArepair #pluripotency #proteostasis #obesity #CellCycle #CellDeath & more!

www.nature.com/ncb/volumes/...

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

We hope this is useful for the field. Our paper can be found here:
www.nature.com/articles/s41...
Or the readcube link below:
rdcu.be/d5gAe
Finally we wish everyone a happy new year!!! 14/end

TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling - Nature Cell Biology

Lu et al. perform systematic functional analyses using data from the TRACERx cohort of patients with non-small-cell lung cancer and delineate how FAT1 regulates homologous recombination repair, chromo...

www.nature.com

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

Finally, a huge thank you to all our funders without which our work would not be possible @crick.ac.uk, Genomics England, @cancerresearchuk.org, @uclh.bsky.social @bcrfcure.bsky.social, Danish Cancer Society, UCL Cancer Institute and @cruk-cityoflondon.bsky.social. 13/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

We thank all our collaborators @mcclellandlab.bsky.social @taponlab.bsky.social @kfugger.bsky.social @nicky Mcgranahan, Nicholas Birbak, Kevin Litchfield and Mariam Jamal-Hanjani. Thank you to the patients and their families, without which we would not be able to start this project. 12/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

This would not be possible w/o the bioinformatics input of @jrmblack.bsky.social @oriolpich.bsky.social Chris Bailey @ruizc.bsky.social, Paco Gimeno-Valiente, Ieva Usaite, Kerstin Thol, Maise Al Bakir & Dhruva Biswas who are dedicated to integrating real-life data with experimental results. 11/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

This work is co-led by @weitinglu.bsky.social and @nnennayakanu.bsky.social lab, with significant input from our long-term collaborator Jiri Bartek . @panoszalmas.bsky.social and high throughput screening core @crick.ac.uk were instrumental in starting this project. 10/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

Now, which of the FAT1 KO phenotypes are due to YAP1 localization? By depleting YAP1 in FAT1 KO cells, we could fully rescue the cytokinesis failure in FAT1 KO. cells, suggesting this is YAP1 dependent. However, the ⏫mitotic error rate was not dependent on YAP1 dysregulation 9/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

How does FAT1 loss lead to its phenotype? We noticed that similar to another key member of the Hippo🦛 pathway LATS1, FAT1 depletion enhances YAP1 nuclear signal. Perhaps LATS1/2 loss contribute to the DDR defects and the phenotypes might be somehow dependent on YAP1? 8/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

How does FAT1 loss cause WGD? Using the FUCCI system in RPE1 cells (thanks to John Diffley lab @crick.ac.uk ) we could track the fidelity of cell division in real-time. The cell without FAT1 failed cytokinesis, could not finish mitosis and remained as 1 daughter cell with 2x the genome content 7/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

We also used live cell imaging to quantify mitotic errors. 6/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

Focusing on CIN, FAT1 loss increased micronuclei formation. FAT1mutant tumours exhibited a higher mutational burden. FAT1 depletion increased ⏫ chromosome number and ⏫radial chromosome structures (blue arrows) and we also observed an⏫ rate of mitotic defects. 5/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

Experimentally, FAT1 depletion reduced ⏬end-resection at DNA double-strand breaks, ⏬HR repair and alternative end-joining, but did not affect cNHEJ. Using TCGA and TRACERx data, we confirmed that FAT1mutant tumours exhibited hallmarks of HR deficiencies like TAI and LST. 4/14

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Wei-Ting Lu @weitinglu.bsky.social · Jan 3

We devised 2 screens to identify drivers that might contribute to both deficiencies in the DNA damage response (DDR) and cause CIN. We focused on a gene called FAT1 (4q35.2), which is extensively mutated/lost in NSCLC before WGD, but we knew little about its function. 3/14

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