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

Sevil Sofueva, Fekret Osman, Alexander Lorenz, Roland Steinacher, Stefania Castagnetti, Jennifer Ledesma, Matthew C. Whitby

Research output: Contribution to journalArticle

44 Citations (Scopus)
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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 characterized 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.
Original languageEnglish
Pages (from-to)6568-6584
Number of pages17
JournalNucleic Acids Research
Volume39
Issue number15
Early online date16 May 2011
DOIs
Publication statusPublished - Aug 2011

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