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

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.

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

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: 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
• Tags: AKR, rivok
• Tags: International impact, Reviewed

Abstract

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