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

TitleA telomerase-associated RecQ protein-like helicase resolves telomeric G-quadruplex structures during replication.
Publication TypeJournal Article
Year of Publication2012
AuthorsPostberg, J., M. Tsytlonok, D. Sparvoli, D. Rhodes, and H. J. Lipps
JournalGene
Volume497
Issue2
Pagination147-54
Date Published2012 Apr 15
ISSN1879-0038
KeywordsAmino Acid Sequence, DNA Helicases, DNA Replication, G-Quadruplexes, Genome, Immunoprecipitation, Macronucleus, Molecular Sequence Data, RecQ Helicases, S Phase, Sporadotrichina, Telomerase, Telomere, Telomere-Binding Proteins
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.

DOI10.1016/j.gene.2012.01.068
Alternate JournalGene
PubMed ID22327026
PubMed Central IDPMC3650557
Grant ListMC_U105184333 / / Medical Research Council / United Kingdom
Research group: