title: Chromatin assembly controls replication fork stability.
abstract: During DNA replication, the advance of replication forks is tightly connected with chromatin assembly, a process that can be impaired by the partial depletion of histone H4 leading to recombinogenic DNA damage. Here, we show that the partial depletion of H4 is rapidly followed by the collapse of unperturbed and stalled replication forks, even though the S-phase checkpoints remain functional. This collapse is characterized by a reduction in the amount of replication intermediates, but an increase in single Ys relative to bubbles, defects in the integrity of the replisome and an accumulation of DNA double-strand breaks. This collapse is also associated with an accumulation of Rad52-dependent X-shaped molecules. Consistently, a Rad52-dependent--although Rad51-independent--mechanism is able to rescue these broken replication forks. Our findings reveal that correct nucleosome deposition is required for replication fork stability, and provide molecular evidence for homologous recombination as an efficient mechanism of replication fork restart.
authors.affiliation: Departamento de Biología Molecular, CABIMER-CSIC, Seville, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Clemente-Ruiz
authors.forename: Félix
authors.initials: F
authors.lastname: Prado
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D000099272:Replisomes
chemical_list: D004259:DNA-Directed DNA Polymerase; D006657:Histones; D009097:Multienzyme Complexes; D000099272:Replisomes