Heterochromatic breaks move to the nuclear periphery to continue recombinational repair.
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.
University of Southern California, Molecular and Computational Biology Department, Los Angeles, California 90089, USA.
Taehyun
T
Ryu
University of Southern California, Molecular and Computational Biology Department, Los Angeles, California 90089, USA.
Brett
B
Spatola
University of Southern California, Molecular and Computational Biology Department, Los Angeles, California 90089, USA.
Laetitia
L
Delabaere
University of Southern California, Molecular and Computational Biology Department, Los Angeles, California 90089, USA.
Katherine
K
Bowlin
University of Southern California, Molecular and Computational Biology Department, Los Angeles, California 90089, USA.
Hannah
H
Hopp
Lawrence Berkeley National Laboratory, Genome Dynamics Department, Berkeley, California 94720, USA.
Ryan
R
Kunitake
Lawrence Berkeley National Laboratory, Genome Dynamics Department, Berkeley, California 94720, USA.|University of California Berkeley, Molecular and Cell Biology Department, Berkeley, California 94720, USA.
Gary H
GH
Karpen
University of Southern California, Molecular and Computational Biology Department, Los Angeles, California 90089, USA.
Irene
I
Chiolo
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D034622:RNA Interference; D059767:Recombinational DNA Repair; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging / Q000379:methods
D029721:Drosophila Proteins; D006570:Heterochromatin; D049452:Green Fluorescent Proteins