Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA

There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10–15% of all human cancers. Tumours...

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Main Authors:	Školáková, Petra, Foldynová-Trantírková, Silvie, Bednářová, Klára, Fiala, Radovan, Vorlíčková, Michaela, Trantírek, Lukáš
Format:	Online
Language:	English
Published:	Oxford University Press 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482068/

id	pubmed-4482068
recordtype	oai_dc
spelling	pubmed-44820682015-06-30 Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA Školáková, Petra Foldynová-Trantírková, Silvie Bednářová, Klára Fiala, Radovan Vorlíčková, Michaela Trantírek, Lukáš Structural Biology There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10–15% of all human cancers. Tumours engaged in the ALT pathway are characterised by the presence of the single stranded 5′-C-rich telomeric overhang (C-overhang). This recently identified hallmark of ALT cancers distinguishes them from healthy tissues and renders the C-overhang as a clear target for anticancer therapy. We analysed structures of the 5′-C-rich and 3′-G-rich telomeric overhangs from human and Caenorhabditis elegans, the recently established multicellular in vivo model of ALT tumours. We show that the telomeric DNA from C. elegans and humans forms fundamentally different secondary structures. The unique structural characteristics of C. elegans telomeric DNA that are distinct not only from those of humans but also from those of other multicellular eukaryotes allowed us to identify evolutionarily conserved properties of telomeric DNA. Differences in structural organisation of the telomeric DNA between the C. elegans and human impose limitations on the use of the C. elegans as an ALT tumour model. Oxford University Press 2015-05-19 2015-04-08 /pmc/articles/PMC4482068/ /pubmed/25855805 http://dx.doi.org/10.1093/nar/gkv296 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Školáková, Petra Foldynová-Trantírková, Silvie Bednářová, Klára Fiala, Radovan Vorlíčková, Michaela Trantírek, Lukáš
spellingShingle	Školáková, Petra Foldynová-Trantírková, Silvie Bednářová, Klára Fiala, Radovan Vorlíčková, Michaela Trantírek, Lukáš Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
author_facet	Školáková, Petra Foldynová-Trantírková, Silvie Bednářová, Klára Fiala, Radovan Vorlíčková, Michaela Trantírek, Lukáš
author_sort	Školáková, Petra
title	Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
title_short	Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
title_full	Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
title_fullStr	Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
title_full_unstemmed	Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
title_sort	unique c. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric dna
description	There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10–15% of all human cancers. Tumours engaged in the ALT pathway are characterised by the presence of the single stranded 5′-C-rich telomeric overhang (C-overhang). This recently identified hallmark of ALT cancers distinguishes them from healthy tissues and renders the C-overhang as a clear target for anticancer therapy. We analysed structures of the 5′-C-rich and 3′-G-rich telomeric overhangs from human and Caenorhabditis elegans, the recently established multicellular in vivo model of ALT tumours. We show that the telomeric DNA from C. elegans and humans forms fundamentally different secondary structures. The unique structural characteristics of C. elegans telomeric DNA that are distinct not only from those of humans but also from those of other multicellular eukaryotes allowed us to identify evolutionarily conserved properties of telomeric DNA. Differences in structural organisation of the telomeric DNA between the C. elegans and human impose limitations on the use of the C. elegans as an ALT tumour model.
publisher	Oxford University Press
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482068/
_version_	1613240669449486336

Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA

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