How does cohesin guide homology search? New preprint from @AlbertoMarinG1 in the @taekjip lab! doi.org/10.1101/2025.02.10.6… New method for monitoring homology search (RaPID-seq)? Check the preprint from the @jcornlab ! doi.org/10.1101/2025.02.10.6…

Congrats to @FedeTeloni and all co-authors! Many thanks to @IMBA_Vienna & the fantastic facilities @viennabiocenter. This work was supported by @ERC_Research , @MSCActions , @FWF_at, @snsf_ch , @EMBO , #WWTF & #BIF. For more great science on this topic check below 👇11/12

We propose a dual function of cohesin in homology search: 🔹Loop-forming cohesin defines search space, limited by TADs 🔹Cohesive cohesin tethers the break to its sister, to favor productive interactions This ensures efficient & accurate homology search! 10/12

DSBs recruit two cohesin pools to distinct domains 🔹Loop-forming cohesin accumulates across ~1 Mb, controlling homology sampling range. 🔹Cohesive cohesin accumulates at DSBs, tethering the broken DNA ends to the intact sister chromatid. 9/12

Cohesion directs homology search towards sister chromatid What happens if we disrupt sister cohesion? Upon sororin depletion (cohesion stabilizer): ✅ Loops remain intact ❌ Contacts between sister chromatids are lost 8/12

DSBs remodel sister chromatids in cis and trans Sister-pore-C allows us to track how DNA architecture changes before and after DSBs. We found that DSBs locally increase loops and interactions between the broken ends and the intact sister chromatid. 7/12

A new tool: sister-pore-C Homology-directed repair normally uses the sister chromatid as a template, but how does a DSB find its sister locus in 3D space? We developed sister-pore-C, a high-resolution method to map chromatin interactions within & between sister chromatids. 6/12

Cohesin-mediated loops control search range When we disrupted cohesin regulators, search dynamics changed: 🔹Reducing loops by NIPBL depletion narrowed homology search 🔹Expanding loops by WAPL depletion made the search broader Cohesin loops regulate homology search range! 5/12

RAD51 filaments sample local TADs By mapping RAD51, a key repair protein, we found that homology search occurs within topologically associated domains near the break rather than across the entire genome. How does chromosome organization influence the search range? 4/12

Site-specific induction of homology-directed repair To study how chromosome architecture influences homology search, we induced DSBs at specific genomic sites in S/G2-synchronized human cells. Most breaks were repaired by homologous recombination. 3/12

The challenge of homology search DNA double-strand breaks (DSBs) are dangerous, but homologous recombination repairs them accurately using a homologous template. How do broken DNA ends find homology sites in the folded chromatin architecture of the nucleus? 2/12

New #preprint from our lab at @IMBA_Vienna ! How do DNA breaks locate homology sites in the vast space of the human genome? We show how #cohesin guides homology search for faithful repair! Read more 👉 tinyurl.com/DSBcohesin Follow along for key insights! 🧵1/12

The Gerlich lab is once again offering a stipended, 9-week Summer School position for undergraduates in 2025 - a chance to join us in Vienna and research chromatin & transcription. For more information, head to training.vbc.ac.at/summer-sc…

Just had our annual lab christmas dinner, featuring curry and Schrottwichteln (a not-quite-secret-santa, rules here: geschenke.de/blogs/wichteln/…). Wishing you a festive end to 2024!

Want to join the Gerlich lab? We are hiring! We are offering a fully funded position in this year's winter call for the @viennabiocenter PhD programme. Apply below ahead of the 15th October deadline #viennawaitsforyou

A great big congratulations to Sofia, who successfully defended her PhD thesis @IMBA_Vienna yesterday. Here’s one happy graduate complete with traditional lab-made defense hat 🎩 Well done Sofia! @SofiaKolesni29 @viennabiocenter @TrainingVbc

This week we waved goodbye to the fantastic Sanne Wijma, who joined our lab as part of the annual @viennabiocenter summer school. Sanne presented her work in yesterday’s summer school symposium, and we couldn’t be more proud!