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A telomerase-associated RecQ protein-like helicase resolves telomeric G-quadruplex structures during replication

Authors :
Daniela Rhodes
Daniela Sparvoli
Maksym Tsytlonok
Jan Postberg
Hans J. Lipps
Source :
Gene
Publication Year :
2012
Publisher :
Elsevier BV, 2012.

Abstract

It is well established that G-quadruplex DNA structures form at ciliate telomeres and their formation throughout the cell-cycle by telomere-end-binding proteins (TEBPs) has been analyzed. During replication telomeric G-quadruplex structure has to be resolved to allow telomere replication by telomerase. It was shown that both phosphorylation of TEBPβ and binding of telomerase are prerequisites for this process, but probably not sufficient to unfold G-quadruplex structure in timely manner to allow replication to proceed. Here we describe a RecQ-like helicase required for unfolding of G-quadruplex structures in vivo. This helicase is highly reminiscent of human RecQ protein-like 4 helicase as well as other RecQ-like helicase found in various eukaryotes and E. coli. In situ analyses combined with specific silencing of either the telomerase or the helicase by RNAi and co-immunoprecipitation experiments demonstrate that this helicase is associated with telomerase during replication and becomes recruited to telomeres by this enzyme. In vitro assays showed that a nuclear extract prepared from cells in S-phase containing both the telomerase as well as the helicase resolves telomeric G-quadruplex structure. This finding can be incorporated into a mechanistic model about the replication of telomeric G-quadruplex structures during the cell cycle.<br />Highlights ► Stylonychia StyRecQL is a helicase reminiscent of human RecQ protein-like 4. ► StyRecQL is enriched in replication band of the macronucleus during S-phase. ► StyRecQL colocalizes and is associated with Tert during telomere replication.

Details

ISSN :
03781119
Volume :
497
Database :
OpenAIRE
Journal :
Gene
Accession number :
edsair.doi.dedup.....9e453bc723eff53b385bc483ab3bfdde
Full Text :
https://doi.org/10.1016/j.gene.2012.01.068