Evidence map›Paper›PMID 39071440›Full record

ArticlebioRxiv : the preprint server for biology2024

"Off-pore" nucleoporins relocalize heterochromatic breaks through phase separation.

Chiara Merigliano, Taehyun Ryu, Colby D See, Christopher P Caridi, Xiao Li, Nadejda L Butova, Trevor W Reynolds, Changfeng Deng, David M Chenoweth, Maya Capelson and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Chiara MeriglianoUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.ORCID 0000-0002-0658-2609
Taehyun RyuHarvard Medical School, Department of Genetics, Boston, MA, USA.
Colby D SeeUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.
Christopher P CaridiUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.
Xiao LiUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.
Nadejda L ButovaUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.
Trevor W ReynoldsUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.
Changfeng DengUniversity of Pennsylvania, Department of Chemistry, School of Arts and Sciences, Philadelphia, PA, USA.
David M ChenowethUniversity of Pennsylvania, Department of Chemistry, School of Arts and Sciences, Philadelphia, PA, USA.
Maya CapelsonSan Diego State University, Department of Biology, San Diego, CA, USA.
Irene ChioloUniversity of Southern California, Molecular and Computational Biology Department, Los Angeles, CA, USA.ORCID 0000-0002-3080-550X

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5M
DROSOPHILA GENOMICS RESOURCE CENTERP40OD010949 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Andrew Zelhof · 2012 to 2026
$9.4M
Roles of nuclear architecture and phase separation in heterochromatin repair dynamicsR01GM117376 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHIOLO, IRENE E · 2015 to 2023
$3.3M
Nuclear Pore Complexes As Scaffolds For Genome Architecture And Epigenetic MaintenanceR01GM124143 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI CAPELSON, MAYA · 2017 to 2025
$3.0M
Understanding the Role of Ulp1 as a clock for heterochromatin repairF31ES036878 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Nadejda Butova · 2024 to 2026
$137k
NIEHS NIH HHS F31 ES036878NIGMS NIH HHS R01 GM117376NIGMS NIH HHS R01 GM124143NIH HHS P40 OD010949NIH HHS P40 OD018537
6 · The paper itself

Abstract

Phase separation forms membraneless compartments in the nuclei, including by establishing heterochromatin "domains" and repair foci. Pericentromeric heterochromatin mostly comprises repeated sequences prone to aberrant recombination, and "safe" homologous recombination (HR) repair of these sequences requires the movement of repair sites to the nuclear periphery before Rad51 recruitment and strand invasion. How this mobilization initiates is unknown, and the contribution of phase separation to these dynamics is unclear. Here, we show that Nup98 nucleoporin is recruited to heterochromatic repair sites before relocalization through Sec13 or Nup88 nucleoporins, and downstream from the Smc5/6 complex and SUMOylation. Remarkably, the phase separation properties of Nup98 are required and sufficient to mobilize repair sites and exclude Rad51, thus preventing aberrant recombination while promoting HR repair. Disrupting this pathway results in heterochromatin repair defects and widespread chromosome rearrangements, revealing a novel "off-pore" role for nucleoporins and phase separation in nuclear dynamics and genome integrity in a multicellular eukaryote.

Indexed as

condensatesdouble-strand break repairHeterochromatin repairhomologous recombinationnuclear architectureNup88Nup98phase separationrepair dynamicsSec13

Identifiers

PMID39071440
PMCPMC11275802

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.