I am very excited to share the newest paper of the lab, a huge amount of work led by our talented PhD student Maxime Galloy, in close collaboration with @Adréanne Blondeau, our dedicated research assistant for 10 years! 🙌

This study revealed an unexpected role for histone macroH2A1.2 ubiquitination in preventing replication fork collapse and RAD18-dependent toxicity during prolonged replication stress. Consequently, when macroH2A1.2 or its ubiquitination is missing, cells become sensitized to specific types of replication stress.

Mechanistically, we show that
• 53BP1 & RAD18 don’t bind nucleosomes with RNF168-ubiquitinated macroH2A1.2 ;

• macroH2A1.2 blocks their recruitment to certain loci under stress ;

• Disruption of macroH2A1.2 ubiquitination led to toxic accumulation of RAD18 foci ;

• RAD18 buildup at collapsed forks is MUS81 dependent.

🙏 Huge thanks to our collaborators: @AlexandreMaréchal, @KyleMMiller, @NitikaTaneja, @JeanYvesMasson, and our institutions @crchuqc @CRC_ULaval @UniversitéLaval @PROTEO.

💡 Special thanks to @AlexandreMaréchal for inspiring and collaborative discussions on replication stress at every stage of this work! And all the members of AFT Lab that participated directly (@elodieVion and Elise Gaudreau-Lavoie) and indirectly in this publication!

https://www.cell.com/molecular-cell/abstract/S1097-2765(25)00614-