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

41 Citations (Scopus)
4 Downloads (Pure)

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

Fingerprint

Anaphase
Genetic Recombination
Chromosomes
Chromatids
Double-Stranded DNA Breaks
G2 Phase
DNA
Eukaryota
DNA Replication
S Phase
Mitosis
Genome
Proteins
Ultrafine

Cite this

Sofueva, S., Osman, F., Lorenz, A., Steinacher, R., Castagnetti, S., Ledesma, J., & Whitby, M. C. (2011). Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier. Nucleic Acids Research, 39(15), 6568-6584. https://doi.org/10.1093/nar/gkr340

Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier. / Sofueva, Sevil; Osman, Fekret; Lorenz, Alexander; Steinacher, Roland; Castagnetti, Stefania; Ledesma, Jennifer; Whitby, Matthew C.

In: Nucleic Acids Research, Vol. 39, No. 15, 08.2011, p. 6568-6584.

Research output: Contribution to journalArticle

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, vol. 39, no. 15, pp. 6568-6584. https://doi.org/10.1093/nar/gkr340
Sofueva, Sevil ; Osman, Fekret ; Lorenz, Alexander ; Steinacher, Roland ; Castagnetti, Stefania ; Ledesma, Jennifer ; Whitby, Matthew C. / Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier. In: Nucleic Acids Research. 2011 ; Vol. 39, No. 15. pp. 6568-6584.
@article{471a2ae3692941b29c2c3a09413fa869,
title = "Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier",
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.",
author = "Sevil Sofueva and Fekret Osman and Alexander Lorenz and Roland Steinacher and Stefania Castagnetti and Jennifer Ledesma and Whitby, {Matthew C.}",
year = "2011",
month = "8",
doi = "10.1093/nar/gkr340",
language = "English",
volume = "39",
pages = "6568--6584",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "15",

}

TY - JOUR

T1 - Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier

AU - Sofueva, Sevil

AU - Osman, Fekret

AU - Lorenz, Alexander

AU - Steinacher, Roland

AU - Castagnetti, Stefania

AU - Ledesma, Jennifer

AU - Whitby, Matthew C.

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80051632086&partnerID=8YFLogxK

U2 - 10.1093/nar/gkr340

DO - 10.1093/nar/gkr340

M3 - Article

VL - 39

SP - 6568

EP - 6584

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 15

ER -