title: Mitosis, double strand break repair, and telomeres: a view from the end: how telomeres and the DNA damage response cooperate during mitosis to maintain genome stability.
abstract: Double strand break (DSB) repair is suppressed during mitosis because RNF8 and downstream DNA damage response (DDR) factors, including 53BP1, do not localize to mitotic chromatin. Discovery of the mitotic kinase-dependent mechanism that inhibits DSB repair during cell division was recently reported. It was shown that restoring mitotic DSB repair was detrimental, resulting in repair dependent genome instability and covalent telomere fusions. The telomere DDR that occurs naturally during cellular aging and in cancer is known to be refractory to G2/M checkpoint activation. Such DDR-positive telomeres, and those that occur as part of the telomere-dependent prolonged mitotic arrest checkpoint, normally pass through mitosis without covalent ligation, but result in cell growth arrest in G1 phase. The discovery that suppressing DSB repair during mitosis may function primarily to protect DDR-positive telomeres from fusing during cell division reinforces the unique cooperation between telomeres and the DDR to mediate tumor suppression.
authors.affiliation: Children's Medical Research Institute, Genome Integrity Group, Westmead, NSW, Australia; University of Sydney, Sydney Medical School, Sydney, NSW, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cesare
mesh_terms: D002843:Chromatin / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D010766:Phosphorylation; D016615:Telomere / Q000235:genetics*; D000071857:Tumor Suppressor p53-Binding Protein 1; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486521:RNF8 protein, human; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D044767:Ubiquitin-Protein Ligases
keywords: DNA damage response; cell cycle; double strand break repair; mitosis; telomeres