Andrew Deans

New from us in @natrevmcb.nature.com -- @szmyd-radoslaw.bsky.social & @radoncdocgee.bsky.social explore how DNA repair actively shapes cancer cell fate following DNA damage, reframing repair as both a protective process & a driver of treatment response and cell death. www.nature.com/articles/s41...

In case you missed the online advance version, we are now in the latest print issue of EMBO J! www.embopress.org/doi/full/10.... Structural and biochemical investigation of the key activation step in the Fanconi anaemia DNA repair pathway, recognition of branched DNA by FANCM

Image credit: @gloglita.bsky.social‬ @lifescienceeditors.bsky.social‬ captured DynaTag in action: a pA-Tn5 probe (multicoloured) binds an antibody (white), which binds p53 DNA-binding domain (green) on DNA (blue) within 2 nucleosomes

🧪Move over CUT&Tag, there’s a new #TranscriptionFactor mapping method in town.
Our newly developed DynaTag is faster, cleaner, more sensitive than #ChIPseq, #CUT&RUN and #CUT&Tag.
🔗 Our @natcomms.nature.com paper: www.nature.com/articles/s41...
🧵Let’s break down what makes DynaTag so powerful (1/7)

This was my all time favourite conference to attend anywhere in the world. Almost makes me wanna get back into research just so I can attend.

Australian Cell Cycle, DNA repair and Telomere Meeting October 20-22, 2025

Register for the Australian Cell Cycle, DNA Repair & Telomere Meeting in beautiful Melbourne October 19-22, 2025. Plenty of slots for selected abstracts and posters. High praise last time from Piotr Sicinski: "en par with a Gordon conference for science and interaction"
www.australiancellcycle.org

Waiting for reviews: 'This is taking forever!' 😤
Doing reviews: 'Extension please?' 🙃

Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose - Nature Communications Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...

A few years back we discovered a dual hybrid protein modification composed of ADP-ribose dinucleotide and ubiquitin (ADPr-Ub). Now we reveal that ADPr-Ub can be further ubiquitinated by the E3 ubiquitin ligase RNF114!
www.nature.com/articles/s41...

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

Symington lab Preprint: Evidence for asymmetrical resection at replication-associated DSBs:
www.biorxiv.org/content/10.1...

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...

Really cool new cryoEM structure of RAD51 caught in the act of recombination initiation at a D-loop. elifesciences.org/reviewed-pre...

Potent Cyclic Peptide Inhibitors Disrupt the FANCM–RMI Interaction FANCM–RMI is a protein–protein interaction that maintains genome stability during DNA repair events in cancers that rely on the Alternative Lengthening of Telomeres (ALT) pathway for survival. We repo...

💥🛟Wow cyclic peptides are cool! So excited to share a new publication on "Potent Cyclic Peptide Inhibitors Disrupt the FANCM–RMI Interaction". Work led by @yuhenglau.bsky.social to which we contributed structures and ideas. The top hits mimic native MM2...but in reverse! pubs.acs.org/doi/10.1021/...

BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability With detailed structural and molecular analyses, Longo et al. find that the BRCA2 C-terminal TR2, which is a critical cancer therapy resistance factor, reshapes the RAD51 dimer for B-DNA binding that ...

BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability: Molecular Cell www.cell.com/molecular-ce...

Andrew Deans @genomestability.bsky.social and collaborators show that #FANCM helicase has evolved from an ancient repair motor into a specialized sensor coupling DNA-damage recognition to Fanconi Anemia pathway activation
www.embopress.org/doi/full/10....

Structural basis of Fanconi anemia pathway activation by FANCM | The EMBO Journal imageimageFANCM employs a sophisticated dual recognition mechanism in genome maintenance, using distinct DNA-binding domains to identify and move around on branched DNA structures. This study reveals how FANCM evolved from an ancient repair motor ...

FANCM is a promising cancer therapeutic target due to genetic interactions with BRCA1, SMARCAL1 & RAD52 & in ALT-positive cancers. Moving toward this goal, our work was an amazing collaboration with industry and academic partners across Australia, China and the UK!
www.embopress.org/doi/full/10....

Instead, a different part of FANCM is required, the MM1 domain. We used AlphaFold modelling to show that the MM1 domain grabs onto the FA core complex binding and mutants in this domain also fail to repair DNA damage properly.

Structure-specific DNA binding, not ATP hydrolysis, is required for FANCD2:FANCI monoubiquitination.

🧩 We also have a new structure of FANCM-CTD:FAAP24, also co-crystallised with splayed DNA. The two ends of the protein cooperative in recognition of branched DNA substrates at replication forks and other DNA junctions.

But FANCM arranges itself on DNA very differently. Using a brand new DNA migration assay we show that several key DNA-binding residues contact the DNA junction (green), while others (yellow) grab onto the splayed DNA so that ATP hydrolysis is converted to forward momentum.

Actually, the protein has evolved from the same ancestor as the dsRNA immune receptor proteins RIG-I and MDA-5, and the siRNA processing enzyme Dicer, and the DNA repair protein XPF.

And here is what FANCM translocase domain bound to 3'flap hairpin DNA looks like!

Using our complete biochemical reconstitution system, we show that FANCM stimulates FANCD2/FANCI monoubiquitination by FA core complex in DNA structure-dependent manner. It promotes stable clamp formation even with USP1:UAF1 deubiquitinase present.

🧬 New from crystal structures from our lab in EMBO Journal! We reveal how the FANCM enzyme, an emerging therapeutic target it cancer, has evolved to specifically recognise branched DNA and activate the Fanconi anaemia pathway of DNA repair. doi.org/10.1038/s443... 🧵👇

CTC1-STN1-TEN1 controls DNA break repair pathway choice via DNA end resection blockade Antagonistic activities of the 53BP1 axis and the tumor suppressor BRCA1-BARD1 determine whether DNA double-strand breaks (DSBs) are repaired by end joining or homologous recombination. We show that t...

CST complex blocks end resection by BLM-DNA2 or EXO1, therefore promoting non-homologous endjoining and inhibiting repair templated DNA repair.
www.science.org/doi/10.1126/...

Due to great enthusiasm, we are extending the early bird registration deadline, at a reduced rate, until 25 May. After this date, the rate will increase by 1500NOK (approx. 135USD). We look forward to seeing you in Trondheim! www.endodnadamage.com

NHMRC has decided to replace the standard scale of 1-7 with something a bit more nuanced for the next round of Investigator grants. Score descriptors to be released soon.

I'm super excited to announce that registrations are now open for the 19th Australian Cell Cycle, DNA Repair and Telomere Workshop. Awesome international speaker line-up, with plenty of locals being invited! Book now to secure your earlybird rate. www.australiancellcycle.org

Some seriously nice biochemistry and cryo-EM of FAN1-PCNA-flapDNA complexes! www.nature.com/articles/s41...

Excited to share our latest from my postdoc at @mskcancercenter.bsky.social in the Sfeir Lab, in collaboration with the Simon Powell Lab! We uncovered a novel genome repair mechanism in human cells: RNA-templated DNA double-strand break repair (RT-DSBR). (1/5)

Nice data! But rather than a new "genome repair mechanism", isn't this just aberrant repair by a pseudo reverse transcriptase? It's too uncommon to be a true "repair mechanism" like NHEJ or HDR, etc, and cells only use it at a meaningful level when given DNA:RNA hybrid donors (Figs 1-4).

What governs where DNA replication begins in human cells? Here, we show that origins of replication in human DNA are epigenetically specified and that crucially, this epigenetic mark is required for both DNA replication and cell proliferation! @narjournal.bsky.social academic.oup.com/nar/article/...