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      Solving the Telomere Replication Problem

      review-article
      Author(s): , , *
      Editor(s):
      Publication date (Electronic):
      Journal: Genes
      Publisher: MDPI
      Keywords: telomere, telomere replication, G-quadruplex, T-loop, TERRA

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          Abstract

          Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity.

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          Replication dynamics of the yeast genome.

          M. Raghuraman, E. Winzeler, D Collingwood … (2001)
          Oligonucleotide microarrays were used to map the detailed topography of chromosome replication in the budding yeast Saccharomyces cerevisiae. The times of replication of thousands of sites across the genome were determined by hybridizing replicated and unreplicated DNAs, isolated at different times in S phase, to the microarrays. Origin activations take place continuously throughout S phase but with most firings near mid-S phase. Rates of replication fork movement vary greatly from region to region in the genome. The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans.
          Article 0 comments Cited 252 times – based on 0 reviews     Review now
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            DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase.

            Katrin Paeschke, John A Capra, Virginia Zakian (2011)
            G-quadruplex (G4) DNA structures are extremely stable four-stranded secondary structures held together by noncanonical G-G base pairs. Genome-wide chromatin immunoprecipitation was used to determine the in vivo binding sites of the multifunctional Saccharomyces cerevisiae Pif1 DNA helicase, a potent unwinder of G4 structures in vitro. G4 motifs were a significant subset of the high-confidence Pif1-binding sites. Replication slowed in the vicinity of these motifs, and they were prone to breakage in Pif1-deficient cells, whereas non-G4 Pif1-binding sites did not show this behavior. Introducing many copies of G4 motifs caused slow growth in replication-stressed Pif1-deficient cells, which was relieved by spontaneous mutations that eliminated their ability to form G4 structures, bind Pif1, slow DNA replication, and stimulate DNA breakage. These data suggest that G4 structures form in vivo and that they are resolved by Pif1 to prevent replication fork stalling and DNA breakage. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Pif1 family helicases suppress genome instability at G-quadruplex motifs

              Katrin Paeschke, Matthew Bochman, P. Daniela Garcia … (2013)
              The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. We show that exceptionally potent G-quadruplex unwinding is conserved amongst Pif1 helicases. Moreover, Pif1 helicases from organisms separated by >3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast. The G-quadruplex-induced damage generated in the absence of Pif1 helicases led to novel genetic and epigenetic changes. Further, when expressed in yeast, human Pif1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening.
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                Author and article information

                Contributors
                Eishi Noguchi: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Genes (Basel)
                Journal ID (iso-abbrev): Genes (Basel)
                Journal ID (publisher-id): genes
                Title: Genes
                Publisher: MDPI
                ISSN (Electronic): 2073-4425
                Publication date (Electronic): 31 January 2017
                Publication date Collection: February 2017
                Volume: 8
                Issue: 2
                Electronic Location Identifier: 55
                Affiliations
                Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Equipe labélisée Ligue Contre le Cancer, 13273 Marseille, France; laetitia.maestroni@ 123456inserm.fr (L.M.); samah.matmati@ 123456inserm.fr (S.M.)
                Author notes
                [* ]Correspondence: stephane.coulon@ 123456inserm.fr ; Tel.: 33-(0)4-86-97-74-07
                Article
                Publisher ID: genes-08-00055
                DOI: 10.3390/genes8020055
                PMC ID: 5333044
                PubMed ID: 28146113
                SO-VID: ed0d9715-8d17-4259-8419-3f58fd4fe101
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 02 November 2016
                Date accepted : 23 January 2017
                Categories
                Subject: Review

                Keywords: telomere,telomere replication,g-quadruplex,t-loop,terra
                Data availability:
                Keywords: telomere, telomere replication, g-quadruplex, t-loop, terra

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