Replication Catastrophe: When a Checkpoint Fails because of Exhaustion
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Replication Catastrophe : When a Checkpoint Fails because of Exhaustion. / Toledo, Luis; Neelsen, Kai John; Lukas, Jiri.
In: Molecular Cell, Vol. 66, No. 6, 15.06.2017, p. 735-749.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Replication Catastrophe
T2 - When a Checkpoint Fails because of Exhaustion
AU - Toledo, Luis
AU - Neelsen, Kai John
AU - Lukas, Jiri
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under increased DNA replication stress.
AB - Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under increased DNA replication stress.
KW - Animals
KW - Cell Death
KW - Cell Proliferation
KW - DNA
KW - DNA Damage
KW - DNA Repair
KW - DNA Replication
KW - Genomic Instability
KW - Humans
KW - Neoplasms
KW - Replication Protein A
KW - Journal Article
KW - Review
U2 - 10.1016/j.molcel.2017.05.001
DO - 10.1016/j.molcel.2017.05.001
M3 - Review
C2 - 28622519
VL - 66
SP - 735
EP - 749
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 6
ER -
ID: 184290876