title: Rif1 Is Required for Resolution of Ultrafine DNA Bridges in Anaphase to Ensure Genomic Stability.
abstract: Sister-chromatid disjunction in anaphase requires the resolution of DNA catenanes by topoisomerase II together with Plk1-interacting checkpoint helicase (PICH) and Bloom's helicase (BLM). We here identify Rif1 as a factor involved in the resolution of DNA catenanes that are visible as ultrafine DNA bridges (UFBs) in anaphase to which PICH and BLM localize. Rif1, which during interphase functions downstream of 53BP1 in DNA repair, is recruited to UFBs in a PICH-dependent fashion, but independently of 53BP1 or BLM. Similar to PICH and BLM, Rif1 promotes the resolution of UFBs: its depletion increases the frequency of nucleoplasmic bridges and RPA70-positive UFBs in late anaphase. Moreover, in the absence of Rif1, PICH, or BLM, more nuclear bodies with damaged DNA arise in ensuing G1 cells, when chromosome decatenation is impaired. Our data reveal a thus far unrecognized function for Rif1 in the resolution of UFBs during anaphase to protect genomic integrity.
authors.affiliation: Department of Molecular Cancer Research, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
authors.forename: Rutger C C
authors.initials: RC
authors.lastname: Hengeveld
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ Groningen, the Netherlands.
authors.forename: H Rudolf
authors.initials: HR
authors.lastname: de Boer
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ Groningen, the Netherlands.
authors.forename: Pepijn M
authors.initials: PM
authors.lastname: Schoonen
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ Groningen, the Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.affiliation: Department of Molecular Cancer Research, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: s.m.a.lens@umcutrecht.nl.
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: Lens
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ Groningen, the Netherlands.
authors.forename: Marcel A T M
authors.initials: MA
authors.lastname: van Vugt
mesh_terms: D000705:Anaphase; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002842:Chromatids; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D016193:G1 Phase; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D048631:Micronucleus, Germline / Q000378:metabolism; D021381:Protein Transport; D034501:Telomere-Binding Proteins / Q000378:metabolism*
chemical_list: C492743:Rif1 protein, human; D034501:Telomere-Binding Proteins; D004247:DNA; D016203:CDC2 Protein Kinase