1. Heterochromatic breaks move to the nuclear periphery to continue recombinational repair
- Author
-
Katherine Bowlin, Laetitia Delabaere, Gary H. Karpen, Hannah Hopp, Irene Chiolo, Taehyun Ryu, Ryan Kunitake, and Brett N. Spatola
- Subjects
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 - Abstract
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.
- Published
- 2015
- Full Text
- View/download PDF