The Ino80 chromatin-remodeling enzyme regulates replisome function and stability.
Previous studies have demonstrated essential roles for ATP-dependent chromatin-remodeling and chromatin-modifying enzymes in gene transcription and DNA repair, but few studies have addressed how the replication machinery deals with chromatin. Here we show that the Ino80 remodeling enzyme is recruited to replication origins as cells enter S phase. Inducible degradation of Ino80 shows that it is required continuously for efficient progression of forks, especially when cells are confronted with low levels of replication stress. Furthermore, we show that stalling of replication forks in an ino80 mutant is a lethal event, and that much of the replication machinery dissociates from the stalled fork. Our data indicate that the chromatin-remodeling activity of Ino80 regulates efficient progression of replication forks and that Ino80 has a crucial role in stabilizing a stalled replisome to ensure proper restart of DNA replication.
Papamichos-Chronakis
Manolis
M
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Biotechnology 2, Suite 210, Worcester, Massachusetts 01605, USA.
Peterson
Craig L
CL
D000074183:ATPases Associated with Diverse Cellular Activities; D002843:Chromatin / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D006918:Hydroxyurea; D009154:Mutation; D016196:S Phase
D002843:Chromatin; D004268:DNA-Binding Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C524421:INO80 protein, human; D006918:Hydroxyurea