Lab blog

1 May 2021, Is it all about DNA Replication forks?

In our latest review paper, Jess and I have examined the available functional and phenotypic data on DNA2 and offer our perspective on why the protein is essential for cell survival and linked to human disease.

 

Our article is part of the Special Issue "DNA Replication Stress and Chromosomal Instability" in the International Journal of Molecular Sciences.

 

 

10 September 2020, DNA2 to the rescue

You can now read our latest opinion piece describing why we think Dna2 is essential by limiting homologous-recombination restart at stalled DNA replication forks, published today with Springer Nature in the journal Current Genetics.

In essence, we propose that Dna2 protects cells from toxic levels of abortive recombination intermediates that lead to DNA damage-checkpoint activation and terminal cell-cycle arrest. These new insights disambiguate the effects of DNA2 dysfunction on cell survival, and provide a framework to rationalize the association of DNA2 with cancer and the primordial dwarfism disorder Seckel syndrome based on its role in replication fork recovery.

 

 

1 September 2020, Owen starts his new job with the NHS

This is us marking Owen's last day in the lab with a hike along the South Downs Way. Owen is off to London today to start his career with the NHS.

Thanks to Owen for all his good work at the Genome Centre and the best of luck for the future from all of us! Never a more important time to be working for the Health Service!

 

 

26 June 2020, To survive, recombination in replication maintenance must be limited

In our latest paper, we show that Dna2’s role in DNA replication fork recovery is essential for cell survival. It turns out Dna2 acts as a key gatekeeper at stalled DNA replication forks to ensure chromosome replication is faithfully completed by fork convergence while limiting replication restart via homologous recombination. In the absence of Dna2, promiscuous use of recombination results in toxic levels of recombination by-products, checkpoint-mediated cell-cycle arrest and cell death. These findings reveal a novel mechanism of cell death in replication-compromised cells and provide a framework to better understand the involvement of DNA2 in cancer and primordial dwarfism (Seckel syndrome).

Congratulations to Benoît and all involved in this work. It changes the perspective on an important and disease-relevant genome caretaker protein and has revealed some really interesting new aspect of replication maintenance, a most fundamental process of cell biology!

 

17 June 2020, Jessica Hudson has joined the lab

Fantastic news that Jess is now in the team! Jess has joined us from the Sussex Drug Discovery Centre where she has worked on targeting genome caretaker proteins in human disease. She has many years of experience in the field of genome stability and will be working on translational projects trying to exploit DNA replication stress and DNA repair defects as potential new anti-cancer strategies!

After all those weeks of Corona virus lock-down, it's great to be back in the lab and to have you with us!

 

 

 

 

 

29 October 2019, Benoît Falquet successfully defends PhD Thesis

Back in Basel, Ben successfully passed his PhD viva at the FMI with flying colours!

Ben has been investigating the role of helicases and nucleases in the cellular response to DNA replication stress, making important contributions to the field along the way. Science is his passion!

Many congratulations!

 

 

 

 

 

 

28 October 2019, Academy of Medical Sciences Professorship awarded

I am extremely grateful to the Academy of Medical Sciences for awarding me a Professorship Award that will support our research over the coming years!

The Professorship scheme is generously supported by the Department of Business, Energy and Industrial Strategy (BEIS), and will allow us to research new ways of selectively killing cancer cells by interfering with DNA repair and replication.

Interested? Watch this space for upcoming job opportunities!

 

 

21 August 2019, How to compartmentalize DNA repair

You can now read our Author's View opinion piece diccussing our recent findings on Rif1 S-acylation. Rif1 S-acylation provides a novel mechanism to compartmentalize DNA double-strand break repair pathway choice in the cell's nucleus.

 

 

 

 

 

15 July 2019, Rowin Appanah has joined the lab

It's a great pleasure to now have Rowin in our team! Rowin joined at the beginning of the month after completing his PhD in Giacomo de Piccoli's lab at Warwick Medical School where he studied the structure and function of the replisome. He is now keen to look at the role of replisome components in DNA replication fork recovery and is already getting his hands wet in the lab!

Welcome to the team!

 

 

 

 

 

10 June 2019, Protein fatty acylation implicated in a DNA repair process for the first time

Just out in @NatureComms, our article identifies Rif1 S-acylation as a mechanism that compartmentalizes DNA double-strand break repair in the nucleus.

You can read the paper here.

Well done Gabri, Daniel, Julia, Stefano et al.!

 

 

3 June 2019, Owen Addis joins the lab

After completing his PhD research project in Chris Chan's lab, Owen joins as a Postdoctoral Research Fellow and wants to explore the links between DNA replication stress, chromosome instability and cancer.

Owen is a microscopy specialist and expert in chromosome segregation. You can see some of his previous work here.

 

So pleased to welcome Owen to the team!

 

 

 

19 March 2019, Ben's review on structure-specific endonucleases published

You can read up on how MUS81, SLX1-4, and GEN1 contribute to genome stability in our article Structure-Specific Endonucleases and the Resolution of Chromosome Underreplication. This review is part of a Genes Special Issue, edited by Dana Branzei, containing plenty of interesting research papers and reviews. Do have a look: Chromosome Replication and Genome Integrity

 

4 February 2019, David Jones joins the lab

David has done his Msc project on Tof1/Timeless and DNA topological stress in Jon Baxter's lab. He comes well prepared for a PhD in cellular responses to replication stress.

Welcome David!

 

 

21 January 2019, Freedom of Movement

A new single-molecule study in Nature Chemical Biology reveals that Holliday junction resolvases can relax their grip on Holliday junctions, allowing them to undergo conformer exchange and branch migration with interesting implications for homologous recombination.

Read about it here and access the original article.

 

4 October 2018, Gabriele awarded FMI's Chiquet-Ehrismann Originality Prize

Congratulations to Gabriele Fontana and Daniel Hess for being awarded the Chiquet-Ehrismann Originality Prize at this year's FMI Annual Meeting. Ruth Chiquet-Ehrismann was a Senior Group Leader at the FMI and Adjunct Professor of the University of Basel who was never afraid to think outside the box and challenge commonly accepted dogma.

The prize recognizes Gabriele's and Daniel's innovative work on genome stability factor Rif1. Well done!