uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Insights into diseases of human telomerase from dynamical modeling
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. (Flores)
2013 (English)In: / [ed] Russ Altman, 2013, 200-211 p.Conference paper, Published paper (Refereed)
Abstract [en]

Mutations in the telomerase complex disrupt either nucleic acid binding or catalysis, and are the cause of numerous human diseases. Despite its importance, the structure of the human telomerase complex has not been observed crystallographically, nor are its dynamics understood in detail. Fragments of this complex from Tetrahymena thermophila and Tribolium castaneum have been crystallized. Biochemical probes provide important insight into dynamics. In this work we summarize evidence that the T. castaneum structure is Telomerase Reverse Transcriptase. We use this structure to build a partial model of the human Telomerase complex. The model suggests an explanation for the structural role of several disease-associated mutations. We then generate a 3D kinematic trajectory of telomere elongation to illustrate a "typewriter" mechanism: the RNA template moves to keep the end of the growing telomeric primer in the active site, disengaging after every 6-residue extension to execute a "carriage return" and go back to its starting position. A hairpin can easily form in the primer, from DNA residues leaving the primer-template duplex. The trajectory is consistent with available experimental evidence. The methodology is extensible to many problems in structural biology in general and personalized medicine in particular.

Place, publisher, year, edition, pages
2013. 200-211 p.
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-187591DOI: 10.1142/9789814447973_0020ISBN: 978-981-4447-97-3 (print)OAI: oai:DiVA.org:uu-187591DiVA: diva2:575247
Conference
Pacific Symposium on Biocomputing
Funder
eSSENCE - An eScience CollaborationSwedish Research Council
Available from: 2012-12-08 Created: 2012-12-08 Last updated: 2013-11-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Flores, Samuel

Search in DiVA

By author/editor
Flores, Samuel
By organisation
Department of Cell and Molecular Biology
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
isbn
urn-nbn

Altmetric score

doi
isbn
urn-nbn
Total: 409 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf