Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage
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Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage. / Mankouri, Hocine W; Hickson, Ian D.
In: Molecular Biology of the Cell, Vol. 17, No. 10, 01.10.2006, p. 4473-83.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage
AU - Mankouri, Hocine W
AU - Hickson, Ian D
PY - 2006/10/1
Y1 - 2006/10/1
N2 - Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3, causes impaired S-phase progression and the persistence of abnormal DNA structures (X-shaped DNA molecules) after exposure to methylmethanesulfonate. The impaired S-phase progression is due to a persistent checkpoint-mediated cell cycle delay and can be overridden by addition of caffeine. Hence, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3(Y356F) are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity.
AB - Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3, causes impaired S-phase progression and the persistence of abnormal DNA structures (X-shaped DNA molecules) after exposure to methylmethanesulfonate. The impaired S-phase progression is due to a persistent checkpoint-mediated cell cycle delay and can be overridden by addition of caffeine. Hence, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3(Y356F) are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity.
KW - Alleles
KW - Cell Cycle
KW - DNA Damage
KW - DNA Replication
KW - Metronidazole
KW - Models, Biological
KW - Rad51 Recombinase
KW - RecQ Helicases
KW - Recombination, Genetic
KW - S Phase
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
U2 - 10.1091/mbc.E06-06-0516
DO - 10.1091/mbc.E06-06-0516
M3 - Journal article
C2 - 16899506
VL - 17
SP - 4473
EP - 4483
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 10
ER -
ID: 33752886