fedeteloni.bsky.social
Postdoc fellow in the @gerlichlab.bsky.social
• http://mas.to/@FeTe • Genomic integrity and nuclear processes • He/him
https://orcid.org/0000-0003-0953-8010
20 posts
249 followers
272 following
Getting Started
Conversation Starter
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Fixed link www.biorxiv.org/content/10.1...
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Thanks Jeroen!
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Yes, after replication sisters are linked by cohesion, making them the preferred template for HR: this restricts the area of search, but additionally we observe that loop-forming and cohesive cohesin work together to define a proper search domain and establish productive contacts
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doi.org/10.1101/2025...
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The study is specific for homologous search of HR during S/G2 phase, we didn't take a look at meiosis yet, but definitely something interesting to pursue.
(Thanks for the DOI heads up, bluesky cut in the preview and it went unnoticed)
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How does cohesin guide homology search? Preprint from @albertomarin.bsky.social in the Ha lab! https://doi.org/10.1101/2025.02.10.637451
New method for monitoring homology search (RaPID-seq)? Preprint from @charlesyeh.bsky.social in @jcornlab.bsky.social! https://doi.org/10.1101/2025.02.10.63716
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Huge thanks to my co-authors, @imbavienna.bsky.social and the fantastic facilities at @viennabiocenter.bsky.social. This work was supported by @erc.europa.eu, #MSCA, @fwf-at.bsky.social, @snsf-ch.bsky.social, @embo.org, @wwtf.at & #BIF.
For more great science on this topic check the post below 👇
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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 favour productive interactions
This ensures efficient & accurate homology search!
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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
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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.
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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.
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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!
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RAD51 filaments sample local TADs
By mapping RAD51, a key repair protein, we found that homology search occurs within topologically associated domains near the breakrather than across the entire genome.
How does chromosome organization influence the search range?
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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.
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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?
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You never know what people might find valuable these days, I guess willhaben is the way!
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Looks like a "portable" speaker system for old iPods! Almost a relic 😂
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Just landed here too :)