Sofueva, S;
Osman, F;
Lorenz, A;
Steinacher, R;
Castagnetti, S;
Ledesma, J;
Whitby, MC;
(2011)
Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier.
Nucleic Acids Research
, 39
(15)
6568- 6584.
10.1093/nar/gkr340.
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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 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.
| Type: | Article |
|---|---|
| Title: | Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/nar/gkr340 |
| Publisher version: | http://dx.doi.org/10.1093/nar/gkr340 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | yeast schizosaccharomyces-pombe, mitotic intrachromosomal recombination, gross chromosomal rearrangements, promotes genomic instability, double-strand breaks, fission yeast, saccharomyces-cerevisiae, homologous recombination, genetic requirements, repair |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1308105 |
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