Heterochromatic breaks move to the nuclear periphery to continue recombinational repair
| Autor: | Katherine Bowlin, Laetitia Delabaere, Gary H. Karpen, Hannah Hopp, Irene Chiolo, Taehyun Ryu, Ryan Kunitake, Brett N. Spatola |
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| Rok vydání: | 2015 |
| Předmět: |
Heterochromatin
Blotting Western Green Fluorescent Proteins SUMO protein Biology Time-Lapse Imaging Article Cell Line 03 medical and health sciences medicine Animals Drosophila Proteins Inner membrane DNA Breaks Double-Stranded Ectopic recombination Strand invasion Nuclear pore In Situ Hybridization Fluorescence 030304 developmental biology Cell Nucleus 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction fungi 030302 biochemistry & molecular biology Recombinational DNA Repair Cell Biology Cell biology Cell nucleus Drosophila melanogaster medicine.anatomical_structure Mutation RNA Interference Homologous recombination |
| Zdroj: | Nature cell biology |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb3258 |
| Popis: | Heterochromatin mostly comprises repeated sequences prone to harmful ectopic recombination during double-strand break (DSB) repair. In Drosophila cells, 'safe' homologous recombination (HR) repair of heterochromatic breaks relies on a specialized pathway that relocalizes damaged sequences away from the heterochromatin domain before strand invasion. Here we show that heterochromatic DSBs move to the nuclear periphery to continue HR repair. Relocalization depends on nuclear pores and inner nuclear membrane proteins (INMPs) that anchor repair sites to the nuclear periphery through the Smc5/6-interacting proteins STUbL/RENi. Both the initial block to HR progression inside the heterochromatin domain, and the targeting of repair sites to the nuclear periphery, rely on SUMO and SUMO E3 ligases. This study reveals a critical role for SUMOylation in the spatial and temporal regulation of HR repair in heterochromatin, and identifies the nuclear periphery as a specialized site for heterochromatin repair in a multicellular eukaryote. |
| Databáze: | OpenAIRE |
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