Jenny Singh

Advancing cancer research via comparative oncology - Nature Reviews Cancer Comparative oncology combines evolutionary biology, ecology, veterinary medicine and clinical oncology to better understand cancer, for example, by identifying the molecular and cellular mechanisms underlying the remarkable cancer resistance of some taxa. Therefore, this Perspective by Vincze et al. calls for the increased use of non-conventional model organisms in cancer research to advance cancer prevention and treatment strategies.

Perspective 🚨
Orsolya Vincze @OVincze, Thomas Pradeu &Co discuss how cancer research can be advanced using comparative oncology and call for the increased use of non-conventional model organisms to advance cancer prevention and treatment.

📖 ⬇️

Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels - preLights Lamin A/C maintains replication fork integrity during mild replication stress by modulating chromatin structure and restraining RECQ1 activity.

First preLights post from Jenny Singh (@jennysingh.bsky.social‬)

She covers work showing that Lamin A/C maintains replication fork integrity during mild replication stress by modulating chromatin structure & restraining RECQ1 activity. #preprint

#preLight ⬇️
prelights.biologists.com/highlights/n...

Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage Protein poly-ADP-ribosylation (PARylation) is a post-translational modification formed by transferring successive units of ADP-ribose to target protei…

Interested in proteins that bind to poly(ADP-ribose)? Check out our recent study here at the Legorreta Cancer Center at Brown University on WWE domains and binding to poly(ADP-ribose) in cells: www.sciencedirect.com/science/arti... @brownuresearch.bsky.social @weldeiry.bsky.social

In this study, Franklin et al. show that histone chaperones, like the transcription-coupled SPT6 and the replication-coupled CAF-1, control cell differentiation and lineage choice through distinct mechanisms. #OpenAccess

Learn more here:
➡️ tinyurl.com/gd352316

A PhD position is open in my group here in Heidelberg. We'll use cool primary cell models of osteosarcoma and genetic screens to understand and overcome mechanisms of clinically acquired drug resistance. It'll be a blast!

karriere.klinikum.uni-heidelberg.de/index.php?ac...

YouTube video by The Company of Biologists spotLights Ep 9: preLights in conversation with Jennifer Richens

Another #spotLights episode is out! 🎙️

Recorded at the #biologists100 conference, @jontytownson.bsky.social talks to Jenny Richens about the preprint she presented (now published @plosbiology.org), the path to preprinting + the benefits of sharing science early.

Listen below ⬇️🎧
youtu.be/eLwGRnBrIaU

PLAMseq enables the proteo-genomic characterization of chromatin-associated proteins and protein interactions in a single experimental workflow. Chromatin Immunoprecipitation (ChIP) and Co-Immunoprecipitation (CoIP) assays are the most common approaches to characterize the genomic localization and protein interactors, respectively, for a prote...

New preprint from the Lab at @cabimer.bsky.social. We present PLAMseq, using TurboID to do like ChIPseq and proximity proteomics in the same protocol with extra powers like mapping protein interactions in the genome.

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

Histone H1 deamidation facilitates chromatin relaxation for DNA repair - Nature Insights into how the linker histone H1 promotes chromatin alterations and allows repair of DNA damage are described.

Nature research paper: Histone H1 deamidation facilitates chromatin relaxation for DNA repair

https://go.nature.com/42iGjda

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...

Can’t wait for this one!

IFI16 senses and protects stalled replication forks Replication stress is a key driver of DNA damage and genome instability. Replication stress-induced fork remodelling generates a new DNA end that is vulnerable to the action of nucleases, and which is...

New preprint from the lab, revealing new roles for IFI16 during replication stress. Great collab with @unterholznerlab.bsky.social and @cejkalab.bsky.social

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

CIP2A is required for mitotic recruitment of the SLX1/XPF/MUS81 tri-nuclease complex to replication stress-induced DNA lesions to maintain genome integrity Perturbed DNA replication can lead to incompletely replicated DNA when cells enter mitosis and can interfere with chromosome segregation. Cells therefore require mechanisms to resolve these lesions du...

Extremely happy to share that my main PhD project about CIP2A-TOPBP1 and the SMX complex is now available online as pre-print.

Huge thanks to all co-authors but especially @marcelvanvugt.bsky.social for giving me the opportunity to work on this exciting project!

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

A chemical-genetic system to rapidly inhibit the PP2A-B56 phosphatase reveals a role at metaphase kinetochores - Nature Communications Phosphatase enzymes are challenging to study due to a lack of specific inhibitors. Here, authors develop a chemical-genetic system to inhibit and characterize a major Ser/Thr phosphatase complex, and ...

Delighted to share a chemical-genetic system we developed to rapidly inhibit a serine/threonine phosphatase complex (within secs). This will make it much easier to study #phosphatases. The system is also applicable to other “undruggable” enzymes.

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

It is maddening how stingy and bureaucratic societies and academic institutions are.

Many expect me to work for free, only offer economy flight tickets, and have me fill out forms for hours.

It is almost as if they do not value science integrity.

I am very thankful to my Patreon supporters!

Diagram of chromatin and nucleosomes from https://www.genome.gov/genetics-glossary/Nucleosome

The DNA in our cells is not naked but instead is compacted by being wrapped around nucleosomes assembled from histone proteins. In our current view, this produces the chromatin architecture that leaves some regions open for transcription while others are more compacted & transcriptionally silent 1/n

Love this

Toward single-molecule protein sequencing using nanopores Nature Biotechnology - Maglia and colleagues discuss advances in nanopore technology en route to single-molecule protein sequencing

Nanopore technology might be able to sequence proteins soon! Read about the road ahead in this exciting Perspective rdcu.be/edWPi in @naturebiotech.bsky.social

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:

On my way to the South of France - looking forward to the science ahead 🧬

Rapid delivery of RNase H1 enables replication fork progression under stress independently of R-loop resolution https://www.biorxiv.org/content/10.1101/2025.02.27.640516v1

For all of you who cannot access pubmed, here is a good alternative:
europepmc.org

Heartbreaking chats this week with students thinking of giving up on their dreams of getting a PhD. They worry about getting in PhD programs and careers post PhD. My suggestions: don’t be hasty, think broadly incl EU & Canada, & careers beyond traditional academia. What’re you telling your students?

Translesion-synthesis-mediated bypass of DNA lesions occurs predominantly behind replication forks restarted by PrimPol The bypass of DNA lesions by translesion synthesis (TLS) polymerases is a critical step for DNA damage tolerance, allowing the completion of DNA synth…

Happy to share our new collaboration paper in Cell Reports. We show that translation synthesis in cancer cells occurs predominantly behind the replication fork, to fill ssDNA gaps, rather than to restart stalled replication forks “on the fly”. www.sciencedirect.com/science/arti...

Is anyone aware of an exhaustive list of all human histone PTMs identified?

Something like CST’s, except (1) continuously updated and (2) describing the actual modification (e.g. ‘symmetric dimethylation’, instead of ‘methylation’)…

#epigenetics #biochemisty 🧬🧪

SPO11 dimers are sufficient to catalyse DNA double-strand breaks in vitro - Nature A biochemical system recapitulates the hallmarks of meiotic double-strand break formation, with mouse SPO11 catalysing break formation in the absence of any partners and remaining covalently atta...

🥳Just published @nature.com. Over 25 years after the discovery of SPO11 as the enzyme responsible for initiating meiotic recombination, we finally succeeded in reconstituting its DNA cleavage activity.🧵
www.nature.com/articles/s41...

Insane

🥳 congratulations Leonie

I'm honoured to speak at the upcoming Genome Instability & Cancer Conference, celebrating the legacy of Angelos Constantinou. His pioneering work transformed our understanding of DNA repair. Register now to join us near his home town in France in March! www.tribute2angelos.fr/page/home/

Artificial intelligence is becoming better than humans at scanning animals’ faces for signs of stress and pain. Are more complex emotions next?

Learn more: https://scim.ag/3EO1V7M