Cell · 2024
TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lascaux Pauline, Hoslett Gwendoline, Tribble Sara, Trugenberger Camilla, Antičević Ivan, Otten Cecile, Torrecilla Ignacio, Koukouravas Stelios, Zhao Yichen, Yang Hongbin, Aljarbou Ftoon, Ruggiano Annamaria, Song Wei, Peron Cristiano, Deangeli Giulio, Domingo Enric, Bancroft James, Carrique Loïc, Johnson Errin, Vendrell Iolanda, Fischer Roman, Ng Alvin Wei Tian, Ngeow Joanne, D'Angiolella Vincenzo, Raimundo Nuno, Maughan Tim, Popović Marta, Milošević Ira, Ramadan Kristijan
Аннотация
DNA repair and autophagy are distinct biological processes vital for cell survival. Although autophagy helps maintain genome stability, there is no evidence of its direct role in the repair of DNA lesions. We discovered that lysosomes process topoisomerase 1 cleavage complexes (TOP1cc) DNA lesions in vertebrates. Selective degradation of TOP1cc by autophagy directs DNA damage repair and cell survival at clinically relevant doses of topoisomerase 1 inhibitors. TOP1cc are exported from the nucleus to lysosomes through a transient alteration of the nuclear envelope and independent of the proteasome. Mechanistically, the autophagy receptor TEX264 acts as a TOP1cc sensor at DNA replication forks, triggering TOP1cc processing by the p97 ATPase and mediating the delivery of TOP1cc to lysosomes in an MRE11-nuclease- and ATR-kinase-dependent manner. We found an evolutionarily conserved role for selective autophagy in DNA repair that enables cell survival, protects genome stability, and is clinically relevant for colorectal cancer patients.