Please use this identifier to cite or link to this item: https://ir.swu.ac.th/jspui/handle/123456789/11906
ชื่อเรื่อง: A mechanism for the extension and unfolding of parallel telomeric g-quadruplexes by human telomerase at single-molecule resolution
ผู้แต่ง: Paudel B.P.
Moye A.L.
Assi H.A.
El-Khoury R.
Cohen S.B.
Holien J.K.
Birrento M.L.
Samosorn S.
Intharapichai K.
Tomlinson C.G.
Teulade-Fichou M.-P.
González C.
Beck J.L.
Damha M.J.
van Oijen A.M.
Bryan T.M.
Keywords: alexafluor 555
chloroform
diagnostic agent
dimethyl sulfoxide
dithiothreitol
edetic acid
guanine quadruplex
levodopa
magnesium chloride
polysorbate 20
potassium chloride
sodium tetraborate decahydrate buffer
telomerase
telomerase reverse transcriptase
triton x 100
unclassified drug
Article
chromosomal parameters
circular dichroism
computer simulation
controlled study
crystal structure
DNA binding
fluorescence microscopy
fluorescence resonance energy transfer
fractional anisotropy
gene frequency
genetic association
genomic instability
high performance liquid chromatography
human
human cell
image analysis
liquid chromatography-mass spectrometry
molecular diagnosis
molecular mechanics
molecular model
protein unfolding
telomerase activity assay
telomere
telomere length
thermostability
ultraviolet visible spectroscopy
วันที่เผยแพร่: 2020
บทคัดย่อ: Telomeric G-quadruplexes (G4) were long believed to form a protective structure at telomeres, preventing their extension by the ribonucleoprotein telomerase. Contrary to this belief, we have previously demonstrated that parallel-stranded conformations of telomeric G4 can be extended by human and ciliate telomerase. However, a mechanistic understanding of the interaction of telomerase with structured DNA remained elusive. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) microscopy and bulk-phase enzymology to propose a mechanism for the resolution and extension of parallel G4 by telomerase. Binding is initiated by the RNA template of telomerase interacting with the G-quadruplex; nucleotide addition then proceeds to the end of the RNA template. It is only through the large conformational change of translocation following synthesis that the G-quadruplex structure is completely unfolded to a linear product. Surprisingly, parallel G4 stabilization with either small molecule ligands or by chemical modification does not always inhibit G4 unfolding and extension by telomerase. These data reveal that telomerase is a parallel G-quadruplex resolvase. © 2020, eLife Sciences Publications Ltd. All rights reserved.
URI: https://ir.swu.ac.th/jspui/handle/123456789/11906
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089610831&doi=10.7554%2feLife.56428&partnerID=40&md5=6913b99e1a52d9d25bfda7cb3dcc02ab
ISSN: 2050084X
Appears in Collections:Scopus 1983-2021

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