Contributions of the TEL-patch Amino Acid Cluster on TPP1 to
Telomeric DNA Synthesis by Human Telomerase

J 2015

Contributions of the TEL-patch Amino Acid Cluster on TPP1 to Telomeric DNA Synthesis by Human Telomerase

DALBY, AB, Ctirad HOFR and TR CECH

Basic information

Original name

Contributions of the TEL-patch Amino Acid Cluster on TPP1 to Telomeric DNA Synthesis by Human Telomerase

Authors

DALBY, AB (840 United States of America), Ctirad HOFR (203 Czech Republic, guarantor, belonging to the institution) and TR CECH (840 United States of America)

Edition

Journal of Molecular Biology, LONDON, ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2015, 0022-2836

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.517

RIV identification code

RIV/00216224:14310/15:00081074

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.jmb.2015.01.008

UT WoS

000351798700006

Keywords in English

telomere; telomerase recruitment; DNA substrate-competition; TPP1 TEL-patch; processivity

Abstract

V originále

Telomere maintenance is a highly coordinated process, and its misregulation is linked to cancer and telomere-shortening syndromes. Recent studies have shown that the TEL-patch-a cluster of amino acids on the surface of the shelterin component TPP1-is necessary for the recruitment of telonnerase to the telomere in human cells. However, there has been only basic biochemical analysis of the role of TPP1 in the telomerase recruitment process. Here we develop an in vitro assay to quantitatively measure the contribution of the TEL-patch to telomerase recruitment-binding and extension of the first telomeric repeat. We also demonstrate that the TEL-patch contributes to the translocation step of the telomerase reaction. Finally, our quantitative observations indicate that the TEL-patch stabilizes the association between telomerase and telomeric DNA substrates, providing a molecular explanation for its contributions to telomerase recruitment and action. (C) 2015 Elsevier Ltd. All rights reserved.

Links

GAP205/12/0550, research and development project

Name: Dynamika vzniku shelterinového komplexu

Investor: Czech Science Foundation

LH13054, research and development project

Name: Studium dynamiky telomerových proteinových komplexů zajišťujících stabilitu genomu (Acronym: TeloProtGen)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

DALBY, AB, Ctirad HOFR and TR CECH. Contributions of the TEL-patch Amino Acid Cluster on TPP1 to Telomeric DNA Synthesis by Human Telomerase. Journal of Molecular Biology. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2015, vol. 427, No 6, p. 1291-1303. ISSN 0022-2836. Available from: https://dx.doi.org/10.1016/j.jmb.2015.01.008.

@article{1312758,
   author = {Dalby, AB and Hofr, Ctirad and Cech, TR},
   article_location = {LONDON},
   article_number = {6},
   doi = {http://dx.doi.org/10.1016/j.jmb.2015.01.008},
   keywords = {telomere; telomerase recruitment; DNA substrate-competition; TPP1 TEL-patch; processivity},
   language = {eng},
   issn = {0022-2836},
   journal = {Journal of Molecular Biology},
   title = {Contributions of the TEL-patch Amino Acid Cluster on TPP1 to Telomeric DNA Synthesis by Human Telomerase},
   url = {http://www.sciencedirect.com/science/article/pii/S0022283615000297},
   volume = {427},
   year = {2015}
}

TY  - JOUR
ID  - 1312758
AU  - Dalby, AB - Hofr, Ctirad - Cech, TR
PY  - 2015
TI  - Contributions of the TEL-patch Amino Acid Cluster on TPP1 to Telomeric DNA Synthesis by Human Telomerase
JF  - Journal of Molecular Biology
VL  - 427
IS  - 6
SP  - 1291-1303
EP  - 1291-1303
PB  - ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
SN  - 00222836
KW  - telomere
KW  - telomerase recruitment
KW  - DNA substrate-competition
KW  - TPP1 TEL-patch
KW  - processivity
UR  - http://www.sciencedirect.com/science/article/pii/S0022283615000297
N2  - Telomere maintenance is a highly coordinated process, and its misregulation is linked to cancer and telomere-shortening syndromes. Recent studies have shown that the TEL-patch-a cluster of amino acids on the surface of the shelterin component TPP1-is necessary for the recruitment of telonnerase to the telomere in human cells. However, there has been only basic biochemical analysis of the role of TPP1 in the telomerase recruitment process. Here we develop an in vitro assay to quantitatively measure the contribution of the TEL-patch to telomerase recruitment-binding and extension of the first telomeric repeat. We also demonstrate that the TEL-patch contributes to the translocation step of the telomerase reaction. Finally, our quantitative observations indicate that the TEL-patch stabilizes the association between telomerase and telomeric DNA substrates, providing a molecular explanation for its contributions to telomerase recruitment and action. (C) 2015 Elsevier Ltd. All rights reserved.
ER  -

DALBY, AB, Ctirad HOFR and TR CECH. Contributions of the TEL-patch Amino Acid Cluster on TPP1 to Telomeric DNA Synthesis by Human Telomerase. \textit{Journal of Molecular Biology}. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2015, vol.~427, No~6, p.~1291-1303. ISSN~0022-2836. Available from: https://dx.doi.org/10.1016/j.jmb.2015.01.008.

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