Journal ArticleDOI
Cellular roles of DNA topoisomerases: a molecular perspective.
TLDR
In this review, the cellular roles of these enzymes are examined from a molecular point of view.Abstract:
DNA topoisomerases are the magicians of the DNA world — by allowing DNA strands or double helices to pass through each other, they can solve all of the topological problems of DNA in replication, transcription and other cellular transactions. Extensive biochemical and structural studies over the past three decades have provided molecular models of how the various subfamilies of DNA topoisomerase manipulate DNA. In this review, the cellular roles of these enzymes are examined from a molecular point of view.read more
Citations
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Breast cancer classification and prognosis based on gene expression profiles from a population-based study
Christos Sotiriou,Soek-Ying Neo,Lisa M. McShane,Edward L. Korn,Philip M. Long,Amir A. Jazaeri,Philippe Martiat,Simon Fox,Adrian L. Harris,Edison T. Liu,Edison T. Liu +10 more
TL;DR: Gene expression patterns were found to be strongly associated with estrogen receptor (ER) status and moderately associated with grade, but not associated with menopausal status, nodal status, or tumor size, in an unselected group of 99 node-negative and node-positive breast cancer patients.
Journal ArticleDOI
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.
Journal ArticleDOI
Advances in autism genetics: on the threshold of a new neurobiology
TL;DR: Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme.
Journal ArticleDOI
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.
Journal ArticleDOI
DNA repair pathways as targets for cancer therapy
TL;DR: There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
The double-strand-break repair model for recombination
TL;DR: This work proposes a new mechanism for meiotic recombination, in which events are initiated by double-strand breaks that are enlarged to double- Strand gaps, and postmeiotic segregation can result from heteroduplex DNA formed at the boundaries of the gap-repair region.
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Supercoiling of the DNA template during transcription.
Leroy F. Liu,James C. Wang +1 more
TL;DR: The model provides an explanation for the experimentally observed high degree of negative or positive supercoiling of intracellular pBR322 DNA when DNA topoisomerase I or gyrase is respectively inhibited and in prokaryotes and eukaryotes.
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Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family.
TL;DR: These findings strongly implicate Spo11 as the catalytic subunit of the meiotic DNA cleavage activity and provide direct evidence that the mechanism of meiotic recombination initiation is evolutionarily conserved.
Journal ArticleDOI
The importance of repairing stalled replication forks
Michael M. Cox,Myron F. Goodman,Kenneth N. Kreuzer,David J. Sherratt,Steven J. Sandler,Kenneth J. Marians +5 more
TL;DR: The bacterial SOS response to unusual levels of DNA damage has been recognized and studied for several decades, but pathways for re-establishing inactivated replication forks under normal growth conditions have received far less attention.