Off-pore Nup98 condensates mobilize heterochromatic breaks and exclude Rad51
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
40480227
DOI
10.1016/j.molcel.2025.05.012
PII: S1097-2765(25)00446-0
Knihovny.cz E-zdroje
- Klíčová slova
- Nup88, Nup98 condensates, Sec13, double-strand break repair, droplets, heterochromatin repair, homologous recombination, nuclear dynamics, nucleoplasmic nucleoporins, phase separation,
- MeSH
- chromozomální proteiny, nehistonové metabolismus genetika MeSH
- Drosophila melanogaster * genetika metabolismus MeSH
- dvouřetězcové zlomy DNA MeSH
- heterochromatin * genetika metabolismus MeSH
- homolog proteinu s chromoboxem 5 MeSH
- komplex proteinů jaderného póru * metabolismus genetika MeSH
- proteiny buněčného cyklu metabolismus genetika MeSH
- proteiny Drosophily * metabolismus genetika MeSH
- rekombinační oprava DNA * MeSH
- rekombinasa Rad51 * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chromozomální proteiny, nehistonové MeSH
- heterochromatin * MeSH
- homolog proteinu s chromoboxem 5 MeSH
- komplex proteinů jaderného póru * MeSH
- nuclear pore complex protein 98 MeSH Prohlížeč
- proteiny buněčného cyklu MeSH
- proteiny Drosophily * MeSH
- rekombinasa Rad51 * MeSH
Phase separation forms membraneless compartments, including heterochromatin "domains" and repair foci. Pericentromeric heterochromatin mostly comprises repeated sequences prone to aberrant recombination. In Drosophila cells, "safe" homologous recombination (HR) repair of these sequences requires their relocalization to the nuclear periphery before Rad51 recruitment and strand invasion. How this mobilization initiates is unknown, and the contribution of phase separation is unclear. Here, we show that Nup98 nucleoporin is recruited to repair sites before relocalization by Sec13 or Nup88, and downstream of the Smc5/6 complex and heterochromatin protein 1 (HP1). Remarkably, Nup98 condensates are immiscible with HP1 condensates, and they 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 an "off-pore" role for nucleoporins and phase separation in nuclear dynamics and genome integrity in a multicellular eukaryote.
Department of Biology Faculty of Medicine Masaryk University Kamenice 5 A7 Brno 62500 Czech Republic
Department of Biology San Diego State University San Diego CA 92182 USA
Department of Chemistry University of Pennsylvania Philadelphia PA 19104 USA
Citace poskytuje Crossref.org
