PMID- 25855805 OWN - NLM STAT- MEDLINE DCOM- 20150731 LR - 20181113 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 43 IP - 9 DP - 2015 May 19 TI - Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA. PG - 4733-45 LID - 10.1093/nar/gkv296 [doi] AB - 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. CI - (c) The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. FAU - Skolakova, Petra AU - Skolakova P AD - Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska, 135, 612 65 Brno, Czech Republic. FAU - Foldynova-Trantirkova, Silvie AU - Foldynova-Trantirkova S AD - Central European Institute of Technology, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic Institute of Parasitology, Academy of Sciences of the Czech Republic, Branisovska, 31, 375 05 Ceske Budejovice, Czech Republic. FAU - Bednarova, Klara AU - Bednarova K AD - Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska, 135, 612 65 Brno, Czech Republic Central European Institute of Technology, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic. FAU - Fiala, Radovan AU - Fiala R AD - Central European Institute of Technology, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic. FAU - Vorlickova, Michaela AU - Vorlickova M AD - Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska, 135, 612 65 Brno, Czech Republic Central European Institute of Technology, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic mifi@ibp.cz. FAU - Trantirek, Lukas AU - Trantirek L AD - Central European Institute of Technology, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic lukas.trantirek@ceitec.muni.cz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150408 PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Caenorhabditis elegans/genetics MH - DNA/*chemistry MH - *Evolution, Molecular MH - Humans MH - Nucleic Acid Conformation MH - Telomere/*chemistry PMC - PMC4482068 EDAT- 2015/04/10 06:00 MHDA- 2015/08/01 06:00 PMCR- 2015/04/08 CRDT- 2015/04/10 06:00 PHST- 2015/03/25 00:00 [accepted] PHST- 2015/01/04 00:00 [received] PHST- 2015/04/10 06:00 [entrez] PHST- 2015/04/10 06:00 [pubmed] PHST- 2015/08/01 06:00 [medline] PHST- 2015/04/08 00:00 [pmc-release] AID - gkv296 [pii] AID - 10.1093/nar/gkv296 [doi] PST - ppublish SO - Nucleic Acids Res. 2015 May 19;43(9):4733-45. doi: 10.1093/nar/gkv296. Epub 2015 Apr 8.