DNA repair by Rad52 liquid droplets

• Published in: Nature communications Vol. 11; no. 1; pp. 695 - 8
• Main Authors: Oshidari, Roxanne, Huang, Richard, Medghalchi, Maryam, Tse, Elizabeth Y. W., Ashgriz, Nasser, Lee, Hyun O., Wyatt, Haley, Mekhail, Karim
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.02.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 14; 14/63; 631/208/211; 631/326/193/2484; 631/337/1427/2190; 631/45/612/1229; 631/80/386/1899; 82/83; Cell Nucleus - genetics; Cell Nucleus - metabolism; Clustering; Cooperation; Damage; Deoxyribonucleic acid; DNA; DNA Damage; DNA Repair; DNA, Fungal - genetics; Droplets; Filaments; Genomes; Humanities and Social Sciences; Lesions; Liquid phases; Microtubules; multidisciplinary; Phase separation; Proteins; Rad52 DNA Repair and Recombination Protein - genetics; Rad52 DNA Repair and Recombination Protein - metabolism; Rad52 protein; Repair; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Tubulin; Tubulin - genetics; Tubulin - metabolism; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14546-z

Cellular processes are influenced by liquid phase separation, but its role in DNA repair is unclear. Here, we show that in Saccharomyces cerevisiae , liquid droplets made up of DNA repair proteins cooperate with different types of DNA damage-inducible intranuclear microtubule filaments (DIMs) to promote the clustering of DNA damage sites and maintain genome stability. Rad52 DNA repair proteins at different DNA damage sites assemble in liquid droplets that fuse into a repair centre droplet via the action of petite DIMs (pti-DIMs). This larger droplet concentrates tubulin and projects short aster-like DIMs (aster-DIMs), which tether the repair centre to longer DIMs mediating the mobilization of damaged DNA to the nuclear periphery for repair. Our findings indicate that cooperation between Rad52 liquid droplets and various types of nuclear filaments promotes the assembly and function of the DNA repair centre. Genome dynamics allow cells to repair DNA double-strand breaks (DSBs), which are highly toxic DNA lesions. Here the authors reveal that in S. cerevisiae , Rad52 DNA repair proteins assemble in liquid droplets that work with dynamic nuclear microtubules to relocalize lesions to the nuclear periphery for repair.