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Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier

Authors
Journal
Nucleic Acids Research
0305-1048
Publisher
Oxford University Press
Publication Date
Volume
39
Issue
15
Identifiers
DOI: 10.1093/nar/gkr340
Keywords
  • Genome Integrity
  • Repair And Replication
Disciplines
  • Biology
  • Medicine

Abstract

Most DNA double-strand breaks (DSBs) in S- and G2-phase cells are repaired accurately by Rad51-dependent sister chromatid recombination. However, a minority give rise to gross chromosome rearrangements (GCRs), which can result in disease/death. What determines whether a DSB is repaired accurately or inaccurately is currently unclear. We provide evidence that suggests that perturbing replication by a non-programmed protein–DNA replication fork barrier results in the persistence of replication intermediates (most likely regions of unreplicated DNA) into mitosis, which results in anaphase bridge formation and ultimately to DNA breakage. However, unlike previously characterised replication-associated DSBs, these breaks are repaired mainly by Rad51-independent processes such as single-strand annealing, and are therefore prone to generate GCRs. These data highlight how a replication-associated DSB can be predisposed to give rise to genome rearrangements in eukaryotes.

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