Proteasome-dependent Processing of Topoisomerase I-DNA Adducts into DNA Double Strand Breaks at Arrested Replication Forks
TLDR
It is shown that the formation of replication-dependent DSBs requires the ubiquitin-proteasome pathway in CPT-treated cells, and results support a replication fork collision model in which Top1 cleavage complexes at the arrested replication forks are degraded by proteasome prior to replication fork runoff on the leading strand to generate D SBs.About:
This article is published in Journal of Biological Chemistry.The article was published on 2009-10-09 and is currently open access. It has received 67 citations till now. The article focuses on the topics: Proteasome maturation protein & DNA replication.read more
Citations
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DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
TL;DR: This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors and discusses the common mechanism of action ofTopoisomerase poisons by interfacial inhibition and trapping of topisomerase cleavage complexes.
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Drugging Topoisomerases: Lessons and Challenges
TL;DR: This review discusses how topoisomerase inhibitors kill cells by trapping topoisomersases on DNA rather than by classical enzymatic inhibition, and extends to a novel mechanism of action of PARP inhibitors and could be applied to the targeting of transcription factors.
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All tangled up: how cells direct, manage and exploit topoisomerase function
TL;DR: It is shown that topoisomerase activity is indispensible to cells, but requires the transient breakage of DNA strands, which has been exploited, often for significant clinical benefit, by various exogenous agents that interfere with cell proliferation.
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γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies
TL;DR: Because of its sensitivity, efficiency and mechanistic relevance, the γH2AX assay has great potential as a DNA damage biomarker; however, the technical and epidemiological heterogeneity highlighted in this review infer a necessity for experimental standardization of the assay.
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Poly(ADP-ribose) polymerase and XPF–ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells
TL;DR: The findings indicate the involvement of XPF–ERCC1 in inducing γH2AX response and repairing topoisomerase I-induced DNA damage as an alternative pathway from PARP and tyrosyl-DNA phosphodiesterase 1.
References
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Mechanisms underlying ubiquitination.
TL;DR: Recent findings reveal that all known E3s utilize one of just two catalytic domains--a HECT domain or a RING finger--and crystal structures have provided the first detailed views of an active site of each type.
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DNA topoisomerases: structure, function, and mechanism.
TL;DR: Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the typeIIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes.
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Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I.
TL;DR: It is proposed that camptothecin blocks the rejoining step of the breakage-reunion reaction of mammalian DNA topoisomerase I, which results in the accumulation of a cleavable complex which resembles the transient intermediate proposed for eukaryotic DNATopoisomersase I.
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Cellular roles of DNA topoisomerases: a molecular perspective.
TL;DR: In this review, the cellular roles of these enzymes are examined from a molecular point of view.
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Topoisomerase I inhibitors : camptothecins and beyond
TL;DR: The mechanisms and molecular determinants of tumour response to TOP1 inhibitor are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage.