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Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase

The elongation of single-stranded DNA repeats at the 3′-ends of chromosomes by telomerase is a key process in maintaining genome integrity in eukaryotes. Abnormal activation of telomerase leads to uncontrolled cell division, whereas its down-regulation is attributed to ageing and several pathologies...

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Autores principales: Petrova, Olga A, Mantsyzov, Alexey B, Rodina, Elena V, Efimov, Sergey V, Hackenberg, Claudia, Hakanpää, Johanna, Klochkov, Vladimir V, Lebedev, Andrej A, Chugunova, Anastasia A, Malyavko, Alexander N, Zatsepin, Timofei S, Mishin, Alexey V, Zvereva, Maria I, Lamzin, Victor S, Dontsova, Olga A, Polshakov, Vladimir I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814841/
https://www.ncbi.nlm.nih.gov/pubmed/29294091
http://dx.doi.org/10.1093/nar/gkx1275
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author Petrova, Olga A
Mantsyzov, Alexey B
Rodina, Elena V
Efimov, Sergey V
Hackenberg, Claudia
Hakanpää, Johanna
Klochkov, Vladimir V
Lebedev, Andrej A
Chugunova, Anastasia A
Malyavko, Alexander N
Zatsepin, Timofei S
Mishin, Alexey V
Zvereva, Maria I
Lamzin, Victor S
Dontsova, Olga A
Polshakov, Vladimir I
author_facet Petrova, Olga A
Mantsyzov, Alexey B
Rodina, Elena V
Efimov, Sergey V
Hackenberg, Claudia
Hakanpää, Johanna
Klochkov, Vladimir V
Lebedev, Andrej A
Chugunova, Anastasia A
Malyavko, Alexander N
Zatsepin, Timofei S
Mishin, Alexey V
Zvereva, Maria I
Lamzin, Victor S
Dontsova, Olga A
Polshakov, Vladimir I
author_sort Petrova, Olga A
collection PubMed
description The elongation of single-stranded DNA repeats at the 3′-ends of chromosomes by telomerase is a key process in maintaining genome integrity in eukaryotes. Abnormal activation of telomerase leads to uncontrolled cell division, whereas its down-regulation is attributed to ageing and several pathologies related to early cell death. Telomerase function is based on the dynamic interactions of its catalytic subunit (TERT) with nucleic acids—telomerase RNA, telomeric DNA and the DNA/RNA heteroduplex. Here, we present the crystallographic and NMR structures of the N-terminal (TEN) domain of TERT from the thermotolerant yeast Hansenula polymorpha and demonstrate the structural conservation of the core motif in evolutionarily divergent organisms. We identify the TEN residues that are involved in interactions with the telomerase RNA and in the recognition of the ‘fork’ at the distal end of the DNA product/RNA template heteroduplex. We propose that the TEN domain assists telomerase biological function and is involved in restricting the size of the heteroduplex during telomere repeat synthesis.
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spelling pubmed-58148412018-02-23 Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase Petrova, Olga A Mantsyzov, Alexey B Rodina, Elena V Efimov, Sergey V Hackenberg, Claudia Hakanpää, Johanna Klochkov, Vladimir V Lebedev, Andrej A Chugunova, Anastasia A Malyavko, Alexander N Zatsepin, Timofei S Mishin, Alexey V Zvereva, Maria I Lamzin, Victor S Dontsova, Olga A Polshakov, Vladimir I Nucleic Acids Res Structural Biology The elongation of single-stranded DNA repeats at the 3′-ends of chromosomes by telomerase is a key process in maintaining genome integrity in eukaryotes. Abnormal activation of telomerase leads to uncontrolled cell division, whereas its down-regulation is attributed to ageing and several pathologies related to early cell death. Telomerase function is based on the dynamic interactions of its catalytic subunit (TERT) with nucleic acids—telomerase RNA, telomeric DNA and the DNA/RNA heteroduplex. Here, we present the crystallographic and NMR structures of the N-terminal (TEN) domain of TERT from the thermotolerant yeast Hansenula polymorpha and demonstrate the structural conservation of the core motif in evolutionarily divergent organisms. We identify the TEN residues that are involved in interactions with the telomerase RNA and in the recognition of the ‘fork’ at the distal end of the DNA product/RNA template heteroduplex. We propose that the TEN domain assists telomerase biological function and is involved in restricting the size of the heteroduplex during telomere repeat synthesis. Oxford University Press 2018-02-16 2017-12-23 /pmc/articles/PMC5814841/ /pubmed/29294091 http://dx.doi.org/10.1093/nar/gkx1275 Text en © The Author(s) 2017. 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
spellingShingle Structural Biology
Petrova, Olga A
Mantsyzov, Alexey B
Rodina, Elena V
Efimov, Sergey V
Hackenberg, Claudia
Hakanpää, Johanna
Klochkov, Vladimir V
Lebedev, Andrej A
Chugunova, Anastasia A
Malyavko, Alexander N
Zatsepin, Timofei S
Mishin, Alexey V
Zvereva, Maria I
Lamzin, Victor S
Dontsova, Olga A
Polshakov, Vladimir I
Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase
title Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase
title_full Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase
title_fullStr Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase
title_full_unstemmed Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase
title_short Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase
title_sort structure and function of the n-terminal domain of the yeast telomerase reverse transcriptase
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814841/
https://www.ncbi.nlm.nih.gov/pubmed/29294091
http://dx.doi.org/10.1093/nar/gkx1275
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