Dirk Remus

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

Torsion is a Dynamic Regulator of DNA Replication Stalling and Reactivation The inherent helical structure of DNA dictates that a replisome must rotate relative to DNA during replication, presenting inevitable topological challenges to replication. However, little is known ab...

If you have not already, make sure to check out two fantastic recent preprints from the Patel and Wang labs on the same topic investigated using magnetic tweezers and angular optical trapping:
doi.org/10.1101/2024... and doi.org/10.1101/2024...

Real-time imaging of rotation during synthesis by the replisome During chromosome replication, unwinding by the helicase and synthesis by the polymerases can lead to overwinding and supercoiling of DNA. The mechanical consequences of these events and resulting loc...

🚨New preprint🚨We developed a transverse flow imaging approach to directly visualize bacterial replisomes challenged by topological barriers and discovered a fast rotational mode of replisome operation. Fantastic work by thomasmretzer.bsky.social and Hamdan Lab! tinyurl.com/replisomerot...

🔬 New from the Farnung Lab: We established a fully in vitro reconstituted chromatin replication system and report the first cryo-EM snapshots of the human replisome engaging nucleosomes. Brilliant work by @felixsteinruecke.bsky.social with support from @jonmarkert.bsky.social! tinyurl.com/replisome

Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naive pluripotent stem cells Pluripotent stem cells are susceptible to acquiring detrimental epigenetic abnormalities, posing a hurdle to their safe use in biomedical applications. Using pluripotent cells with defined genetic bac...

Our work on the regulation is out www.cell.com/stem-cell-re...! Congrats to our collaborators in the Vierbuchen and Mezey labs. It turns out that genetic variation has to be very much considered if you want to harness stem cells safely in biomedicine. #pluripotency #epigenetics #stemcells

Engineering mtDNA deletions by reconstituting end joining in human mitochondria Recent breakthroughs in the genetic manipulation of mitochondrial DNA (mtDNA) have enabled precise base substitutions and the efficient elimination of…

Combining bacterial end joining with programmable nucleases, we induced mtDNA deletions in human cells at varying heteroplasmy and examined their metabolic and cellular effects. Simple tool to apply across any cell type and engineer pathogenic mtDNA deletions. www.sciencedirect.com/science/arti...

Congrats!!

Cryo-Electron Microscopy Reveals Hidden Mechanics of DNA Replication, Sheds New Light on Cancer Target MSK researchers shed new light on G-quadruplexes, a type of secondary DNA structure that has attracted attention as a potential therapeutic target in cancer.

Shout out to Sloan Kettering @mskcancercenter.bsky.social for supporting basic science / foundational biology...

www.mskcc.org/news/cryo-el...

In our latest preprint, we uncover how CMG helicase overcomes covalent DNA-protein crosslinks. Check out our findings here:
www.biorxiv.org/content/10.1...

G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

Thrilled to share first part of my post-doc work, published today in @science.org www.science.org/doi/10.1126/...
We use reconstituted replication system and cryo-EM to unravel an unexpected mechanism of DNA translocation employed by eukaryotic replicative helicase.

G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

How do replisomes walk on DNA? And what happens when they run into a G-quadruplex? @sahilbatra.bsky.social and @benallwein.bsky.social provide unexpected insight in our latest paper with Richard Hite @mskcancercenter.bsky.social @science.org www.science.org/doi/10.1126/.... Congrats to all authors!

G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

I am so proud to share a major part of my graduate school research, published today in Science, where we use cell-free replication assays and cryo-EM to describe a central mechanism of eukaryotic DNA replication:

www.science.org/doi/10.1126/...

America's Greatest Workplaces for Inclusion & Diversity 2025 Newsweek is partnering with Plant-A Insights Group to honor America's Greatest Workplaces for Inclusion & Diversity 2025. These companies are committed to fostering an inclusive and diverse work envir...

MSK has been recognized as one of the national's top workplaces for inclusion and diversity by @newsweek.com magazine. 🎉

MSK earned five stars, the highest ranking, among mid to large employers in America. Learn more: www.newsweek.com/rankings/ame...

In the midst of all the NIH & NSF chaos, I want to take a moment to focus on some good news and talk about science! 🧬✨

🚨 New preprint alert! 🚨 doi.org/10.1101/2025...
🧵👇 (1/)

Proud to share our latest publication in @narjournal.bsky.social! A fantastic team effort led by @marcelwerner.bsky.social and Manuel T., where we explore the chromatin dynamics at transcription-replication conflicts (TRC) sites and their impact on genome stability using a novel TRC reporter system.

Please check out our preprint where we find that mitotic transcription helps ensure ecDNA inheritance through chromosomal tethering:

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

Setting up shop in advance of closing our profile on X.

Deadline to apply (Feb 10) is quickly approaching. If you are interested in learning about a postdoc opportunity at MSK, don't wait to apply.

Fascinating and thought-provoking new study by Tony Cesare's lab! It was a pleasure to write a News & Views about this work together with @villungerlab.bsky.social
www.nature.com/articles/s41...

New year, new beginnings! 🎉

The Aviram Lab will officially open its doors on March 1st @mskcancercenter.bsky.social!

We’ll study microbial immune systems and their connection to fundamental cellular processes like #RNA transcription and #DNA integrity.

#NewPI #AcademicSky #WomenInSTEM
(1/2)

Happy to share a new work from the lab on how DNA damage checkpoint can be down-regulated. rdcu.be/d5o3E. Congrats to all authors at @mskcancercenter.bsky.social and our Weill BCMB student @tzippora.bsky.social. gradschool.weill.cornell.edu/bcmb-allied-...

Architecture of the 1.3 MDa complex of human UBR4 (2 x UBR4/KCMF1/CALM1). Picture shows top and side views of the cryo-EM density map and the modeled structure, colored by protein components and domains.

🎄 xmas preprint 🎄 we are excited to share our cryo-EM structure of UBR4 in complex with KCMF1 and CALM1. the PQC ligase forms a massive ubiquitination arena, primed to amplify ubiquitin chains (E4 activity) and boost degradation of defective proteins. www.biorxiv.org/content/10.1...

the Lai lab got a holiday gift ... so excited to share Seungjae Lee's work on surprising regulation of miRNA pathway at Science!! he did it all, from molecular genetics to biochemistry to genomics. and amazing collab with Makiko Yasuda lab brought it into mice. 1/3

www.science.org/doi/10.1126/...

Engineered extrachromosomal oncogene amplifications promote tumorigenesis - Nature Large extrachromosomal DNAs are engineered using a CRISPR- and Cre–loxP-based approach and shown to drive cancer in mouse models, with potential applications in determining the role of oncogene a...

🧪1/ 🚨New paper on ecDNAs from our lab!
We reveal a strategy to engineer extrachromosomal DNA (ecDNA) amplifications in cells & mice. Let's dive in! Let’s dive in! 🧵👇
www.nature.com/articles/s41...

It’s a wrap! The final version of our paper is out 🎉 where we characterize the multifaceted response of the transcript-activated type III CRISPR-Cas immunity. Here’s a skytorial (bluetorial?) by my awesome co-lead @akshilton.bsky.social

#RNA #RNAsky #WomenInSTEM

Multiple mechanisms for licensing human replication origins Nature - Biochemical and structural studies of the loading pathway of the human MCM2–7 replicative helicase motor reveal differences from the orthologous yeast system that may increase...

Awesome paper, I think the authors are not on Bluesky yet

Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability - Nature Communications DNA repeats can lengthen or shorten during their replication, which may lead to a human disease. Here, the authors discovered that an essential replication protein, Mcm10, counteracts instability of G...

Another week, another great paper! Kudos to the amazing grad student, Chiara Masnovo who single-handedly initiated and led the project, and arranged a terrific collaboration with the Aharoni lab from Ben-Gurion University, and to the great members of the two labs.

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

Selfie in the new research lab.

Super excited for my first day as Assistant Prof at @cuanschutz.bsky.social in the Dept of Pharmacology! The lab is open, and now I can't wait to do exciting science! #FirstGen #newPI #STEM #AcademicLife #ExcitingScience #PhDLife #WomenInSTEM #MomInSTEM #GenomeStability #CellBiology #DNARepair

genesdev.cshlp.org/content/earl...

It's now out! This work from Hexiao Wang is a real tour de force. The gist is that innate immune sensing in the nucleus may be a mechanism of replication for surveillance. Check it out!