title: Role for hACF1 in the G2/M damage checkpoint.
abstract: Active chromatin remodelling is integral to the DNA damage response in eukaryotes, as damage sensors, signalling molecules and repair enzymes gain access to lesions. A variety of nucleosome remodelling complexes is known to promote different stages of DNA repair. The nucleosome sliding factors CHRAC/ACF of Drosophila are involved in chromatin organization during development. Involvement of corresponding hACF1-containing mammalian nucleosome sliding factors in replication, transcription and very recently also non-homologous end-joining of DNA breaks have been suggested. We now found that hACF1-containing factors are more generally involved in the DNA damage response. hACF1 depletion increases apoptosis, sensitivity to radiation and compromises the G2/M arrest that is activated in response to UV- and X-rays. In the absence of hACF1, γH2AX and CHK2ph signals are diminished. hACF1 and its ATPase partner SNF2H rapidly accumulate at sites of laser-induced DNA damage. hACF1 is also required for a tight checkpoint that is induced upon replication fork collapse. ACF1-depleted cells that are challenged with aphidicolin enter mitosis despite persistence of lesions and accumulate breaks in metaphase chromosomes. hACF1-containing remodellers emerge as global facilitators of the cellular response to a variety of different types of DNA damage.
authors: Adolf-Butenandt-Institute, Ludwig-Maximilians-University Munich, Germany.
authors: Sara
authors: S
authors: Sánchez-Molina
authors: Oliver
authors: O
authors: Mortusewicz
authors: Béatrice
authors: B
authors: Bieber
authors: Susanne
authors: S
authors: Auer
authors: Maren
authors: M
authors: Eckey
authors: Heinrich
authors: H
authors: Leonhardt
authors: Anna A
authors: AA
authors: Friedl
authors: Peter B
authors: PB
authors: Becker
mesh_terms: D016590:Aphidicolin / Q000633:toxicity; D017209:Apoptosis; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D002873:Chromosome Fragility; D004249:DNA Damage; D004260:DNA Repair; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D034622:RNA Interference; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000092468:Bromodomain Containing Proteins
chemical_list: D016590:Aphidicolin; D002868:Chromosomal Proteins, Non-Histone; D014157:Transcription Factors; C492319:BAZ1A protein, human; D000092468:Bromodomain Containing Proteins