Reference - Detail
| RRC ID | 87636 |
|---|---|
| Author | Merigliano C, Ryu T, Cibulka J, Rawal CC, See CD, Mitra A, Reynolds TW, Butova NL, Caridi CP, Li X, Wang J, Deng C, Chenoweth DM, Sung P, Capelson M, Krejčí L, Chiolo I. |
| Title | Off-pore Nup98 condensates mobilize heterochromatic breaks and exclude Rad51. |
| Journal | Mol Cell |
| Abstract |
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. |
| Volume | 85(12) |
| Pages | 2355-2373.e11 |
| Published | 2025-6-19 |
| DOI | 10.1016/j.molcel.2025.05.012 |
| PII | S1097-2765(25)00446-0 |
| PMID | 40480227 |
| PMC | PMC12303331 |
| MeSH | Animals Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Chromobox Protein Homolog 5 Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism DNA Breaks, Double-Stranded Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Heterochromatin* / genetics Heterochromatin* / metabolism Nuclear Pore Complex Proteins* / genetics Nuclear Pore Complex Proteins* / metabolism Rad51 Recombinase* / genetics Rad51 Recombinase* / metabolism Recombinational DNA Repair* |
| IF | 15.584 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Bluesky |
| Total number of mentions | 37 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | DGRC#203684 |