Andrew Deans
@genomestability.bsky.social
Head of Genome Stability Unit at SVI, Melbourne. All things DNA damage response: Fanconi Anaemia, Bloom Syndrome, Gene editing, R-loops, telomeres, HR & more
No, not that FANCL!
New paper on FancL mutant mouse just out in @bloodadvances.bsky.social shows essential function of E3 RING ligase activity to phenotypes of #FanconiAnemia plus, Black Friday deal: a new model for testing gene editing therapies: ashpublications.org/bloodadvance...
New paper on FancL mutant mouse just out in @bloodadvances.bsky.social shows essential function of E3 RING ligase activity to phenotypes of #FanconiAnemia plus, Black Friday deal: a new model for testing gene editing therapies: ashpublications.org/bloodadvance...
November 27, 2025 at 2:04 AM
No, not that FANCL!
New paper on FancL mutant mouse just out in @bloodadvances.bsky.social shows essential function of E3 RING ligase activity to phenotypes of #FanconiAnemia plus, Black Friday deal: a new model for testing gene editing therapies: ashpublications.org/bloodadvance...
New paper on FancL mutant mouse just out in @bloodadvances.bsky.social shows essential function of E3 RING ligase activity to phenotypes of #FanconiAnemia plus, Black Friday deal: a new model for testing gene editing therapies: ashpublications.org/bloodadvance...
Finally! We have a FANCM:RMI inhibitor that is cell active and specifically kills ALT+ cancer cells 🎯
@yuhenglau.bsky.social + my labs just published the first cell-active peptide inhibitors of this critical target in 10-15% of cancers. doi.org/10.1021/acs....
@yuhenglau.bsky.social + my labs just published the first cell-active peptide inhibitors of this critical target in 10-15% of cancers. doi.org/10.1021/acs....
November 17, 2025 at 5:24 AM
Finally! We have a FANCM:RMI inhibitor that is cell active and specifically kills ALT+ cancer cells 🎯
@yuhenglau.bsky.social + my labs just published the first cell-active peptide inhibitors of this critical target in 10-15% of cancers. doi.org/10.1021/acs....
@yuhenglau.bsky.social + my labs just published the first cell-active peptide inhibitors of this critical target in 10-15% of cancers. doi.org/10.1021/acs....
It was a great honour to present the AGCT (Australian Genome instability, Cell cycle and Telomere) award to Prof Kum Kum Khanna yesterday evening at #ADCTM25. Kum Kum has had an amazing career in discoveries relating to these fields in Australia, and been a remarkable leader and mentor to many.
October 22, 2025 at 4:38 AM
It was a great honour to present the AGCT (Australian Genome instability, Cell cycle and Telomere) award to Prof Kum Kum Khanna yesterday evening at #ADCTM25. Kum Kum has had an amazing career in discoveries relating to these fields in Australia, and been a remarkable leader and mentor to many.
Ever wondered what S-phase tastes like? 3 lucky presenter prize winners will find out (+Amazon voucher!) at #ACDTM25. You can still register for this fantastic Melbourne meeting Oct 20-22. Official 10 year old taste tester: "lemon excision repair" is the best flavour www.australiancellcycle.org
October 13, 2025 at 2:25 AM
Ever wondered what S-phase tastes like? 3 lucky presenter prize winners will find out (+Amazon voucher!) at #ACDTM25. You can still register for this fantastic Melbourne meeting Oct 20-22. Official 10 year old taste tester: "lemon excision repair" is the best flavour www.australiancellcycle.org
🚨 Last chance! Register NOW for the Australian Cell Cycle, DNA Repair & Telomere Meeting 🧬
📍 Melbourne Museum | Oct 19–22
Submit your abstract + lock in the reduced rate this week
👉 australiancellcycle.org
📍 Melbourne Museum | Oct 19–22
Submit your abstract + lock in the reduced rate this week
👉 australiancellcycle.org
August 24, 2025 at 10:28 PM
🚨 Last chance! Register NOW for the Australian Cell Cycle, DNA Repair & Telomere Meeting 🧬
📍 Melbourne Museum | Oct 19–22
Submit your abstract + lock in the reduced rate this week
👉 australiancellcycle.org
📍 Melbourne Museum | Oct 19–22
Submit your abstract + lock in the reduced rate this week
👉 australiancellcycle.org
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
July 28, 2025 at 10:19 PM
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
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.
June 2, 2025 at 12:42 AM
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.
June 2, 2025 at 12:42 AM
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.
June 2, 2025 at 12:42 AM
🧩 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.
June 2, 2025 at 12:42 AM
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.
June 2, 2025 at 12:42 AM
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!
June 2, 2025 at 12:42 AM
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.
June 2, 2025 at 12:42 AM
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... 🧵👇
June 2, 2025 at 12:42 AM
🧬 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... 🧵👇
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.
May 19, 2025 at 4:31 AM
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
May 15, 2025 at 5:48 AM
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...
May 15, 2025 at 12:55 AM
Some seriously nice biochemistry and cryo-EM of FAN1-PCNA-flapDNA complexes! www.nature.com/articles/s41...
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/
November 20, 2024 at 12:18 AM
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/
These FANCM mutations had major consequences in ALT-positive cancer cells: they couldn't rescue cell cycle arrest, telomere-associated replication stress, or cell lethality when endogenous FANCM was depleted.
November 23, 2024 at 5:39 AM
These FANCM mutations had major consequences in ALT-positive cancer cells: they couldn't rescue cell cycle arrest, telomere-associated replication stress, or cell lethality when endogenous FANCM was depleted.
When we removed Hel2i or mutated key DNA-binding residues, FANCM's affinity for junction DNA dropped significantly. This also completely abolished its branch migration activity.
November 23, 2024 at 5:32 AM
When we removed Hel2i or mutated key DNA-binding residues, FANCM's affinity for junction DNA dropped significantly. This also completely abolished its branch migration activity.
The Hel2i subdomain within the translocase is the star of the show! 🌟 It's essential for effective DNA binding and couples this binding to ATP-dependent branch migration.
November 23, 2024 at 5:26 AM
The Hel2i subdomain within the translocase is the star of the show! 🌟 It's essential for effective DNA binding and couples this binding to ATP-dependent branch migration.
Was great to have @BenCarrollMP and our @MaddiesVision supporters visit the lab to hear about our latest gene editing projects to cure bone marrow failure syndromes and other genetic disorders. @SVIResearch
November 23, 2024 at 5:26 AM
Was great to have @BenCarrollMP and our @MaddiesVision supporters visit the lab to hear about our latest gene editing projects to cure bone marrow failure syndromes and other genetic disorders. @SVIResearch