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
AN - SCOPUS:80051632086
SN - 0305-1048
VL - 39
SP - 6568
EP - 6584
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 15
ER -