title: ATMIN is required for the ATM-mediated signaling and recruitment of 53BP1 to DNA damage sites upon replication stress.
abstract: Unresolved replication intermediates can block the progression of replication forks and become converted into DNA lesions, hence exacerbating genomic instability. The p53-binding protein 1 (53BP1) forms nuclear bodies at sites of unrepaired DNA lesions to shield these regions against erosion, in a manner dependent on the DNA damage kinase ATM. The molecular mechanism by which ATM is activated upon replicative stress to localize the 53BP1 protection complex is unknown. Here we show that the ATM-INteracting protein ATMIN (also known as ASCIZ) is partially required for 53BP1 localization upon replicative stress. Additionally, we demonstrate that ATM activation is impaired in cells lacking ATMIN and we define that ATMIN is required for initiating ATM signaling following replicative stress. Furthermore, loss of ATMIN leads to chromosomal segregation defects. Together these data reveal that chromatin integrity depends on ATMIN upon exposure to replication-induced stress.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, Waehringer Strasse 13A, 1090 Vienna, Austria.
authors.forename: Luisa
authors.initials: L
authors.lastname: Schmidt
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria.
authors.forename: Marc
authors.initials: M
authors.lastname: Wiedner
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria.
authors.forename: Georgia
authors.initials: G
authors.lastname: Velimezi
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria.
authors.forename: Jana
authors.initials: J
authors.lastname: Prochazkova
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria.
authors.forename: Michel
authors.initials: M
authors.lastname: Owusu
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bauer
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria. Electronic address: jloizou@cemm.oeaw.ac.at.
authors.forename: Joanna I
authors.initials: JI
authors.lastname: Loizou
mesh_terms: D016590:Aphidicolin / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D020090:Chromosome Segregation; D004249:DNA Damage / Q000187:drug effects; D004261:DNA Replication; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C522841:ATMIN protein, human; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; D016590:Aphidicolin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: 53BP1; ATM; ATMIN; Replication stress