title: TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability.
abstract: DNA anaphase bridges are a potential source of genome instability that may lead to chromosome breakage or nondisjunction during mitosis. Two classes of anaphase bridges can be distinguished: DAPI-positive chromatin bridges and DAPI-negative ultrafine DNA bridges (UFBs). Here, we establish budding yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion of TopBP1/Dpb11 led to an accumulation of chromatin bridges. Importantly, the NoCut checkpoint that delays progression from anaphase to abscission in yeast was activated by both UFBs and chromatin bridges independently of Dpb11, and disruption of the NoCut checkpoint in Dpb11-depleted cells led to genome instability. In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination.
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaloeesvej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Germann
authors.forename: Vera
authors.initials: V
authors.lastname: Schramke
authors.forename: Rune Troelsgaard
authors.initials: RT
authors.lastname: Pedersen
authors.forename: Irene
authors.initials: I
authors.lastname: Gallina
authors.forename: Nadine
authors.initials: N
authors.lastname: Eckert-Boulet
authors.forename: Vibe H
authors.initials: VH
authors.lastname: Oestergaard
authors.forename: Michael
authors.initials: M
authors.lastname: Lisby
mesh_terms: D000705:Anaphase / Q000235:genetics*; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D042822:Genomic Instability; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C097185:DPB11 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; C082728:RFA1 protein, S cerevisiae; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases