RETRACTED: Mitosis inhibits DNA double-strand break repair to guard against telomere fusions
- PMID: 24652939
- DOI: 10.1126/science.1248024
RETRACTED: Mitosis inhibits DNA double-strand break repair to guard against telomere fusions
Retraction in
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Retraction.Science. 2025 Jan 10;387(6730):147. doi: 10.1126/science.adv1263. Epub 2025 Jan 9. Science. 2025. PMID: 39787242 No abstract available.
Expression of concern in
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Editorial Expression of Concern.Science. 2024 Dec 6;386(6726):1102. doi: 10.1126/science.adu7951. Epub 2024 Dec 5. Science. 2024. PMID: 39637004 No abstract available.
Abstract
Mitotic cells inactivate DNA double-strand break (DSB) repair, but the rationale behind this suppression remains unknown. Here, we unravel how mitosis blocks DSB repair and determine the consequences of repair reactivation. Mitotic kinases phosphorylate the E3 ubiquitin ligase RNF8 and the nonhomologous end joining factor 53BP1 to inhibit their recruitment to DSB-flanking chromatin. Restoration of RNF8 and 53BP1 accumulation at mitotic DSB sites activates DNA repair but is, paradoxically, deleterious. Aberrantly controlled mitotic DSB repair leads to Aurora B kinase-dependent sister telomere fusions that produce dicentric chromosomes and aneuploidy, especially in the presence of exogenous genotoxic stress. We conclude that the capacity of mitotic DSB repair to destabilize the genome explains the necessity for its suppression during mitosis, principally due to the fusogenic potential of mitotic telomeres.
Comment in
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DNA damage response: Mitosis: don't 'repair' the telomere!Nat Rev Mol Cell Biol. 2014 May;15(5):300. doi: 10.1038/nrm3792. Epub 2014 Apr 9. Nat Rev Mol Cell Biol. 2014. PMID: 24713631 No abstract available.
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Let it go: how to deal with a breakup in mitosis.Nat Struct Mol Biol. 2014 May;21(5):433-5. doi: 10.1038/nsmb.2825. Nat Struct Mol Biol. 2014. PMID: 24799037 No abstract available.
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Keeping 53BP1 out of focus in mitosis.Cell Res. 2014 Jul;24(7):781-2. doi: 10.1038/cr.2014.62. Epub 2014 May 9. Cell Res. 2014. PMID: 24810302 Free PMC article.
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