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Mitosis Inhibits DNA Double-Strand Break Repair to Guard Against Telomere Fusions

2014· article· en· 319 citations· W2076248918 on OpenAlex· 10.1126/science.1248024

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.
Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

Post-publication record

Nature
Retraction
Reason
Concerns/Issues about Data;Concerns/Issues about Image;Investigation by Company/Institution;Investigation by Journal/Publisher;Unreliable Data;Unreliable Results and/or Conclusions;Upgrade/Update of Prior Notice(s);
Date
1/9/2025 0:00
Flagged by OpenAlex?
Yes

Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Science
Topic
DNA Repair Mechanisms
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
University of TorontoLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
Funders
Canadian Institutes of Health Research
Keywords
TelomereMitosisCell biologyBiologyDNAGenetics
Has abstract in OpenAlex
yes