title: Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA.
abstract: In budding yeast, DNA ends are processed by the consecutive action of MRX/Sae2 and two redundant pathways dependent on Sgs1/Dna2 and Exo1, and this processing is counteracted by Ku heterodimer. Here we show that DNA end resection by Sae2 and Sgs1 is dispensable for normal telomere maintenance by telomerase. Instead, these proteins facilitate telomere replication and limit the accumulation of single-strand DNA (ssDNA) at replication fork pause sites. Loss of Sae2 and Sgs1 drives selection for compensatory mutations, notably in Ku, which are responsible for abrupt telomere shortening in cells lacking Sae2 and Sgs1. In telomerase-negative cells, Sae2 and Sgs1 play non-overlapping roles in generating ssDNA at eroded telomeres and are required for the formation of type II survivors. Thus, although their primary function in telomerase-positive cells is to sustain DNA replication over the sites that are prone to fork pausing, Sae2 and Sgs1 contribute to telomere resection in telomerase-deficient cells.
authors.affiliation: Cancer Research Center of Marseille (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University (AMU), Institut Paoli-Calmettes, Marseille F-13009, France. Equipe labellisée Ligue 2014.
authors.forename: Julien
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Cancer Research Center of Marseille (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University (AMU), Institut Paoli-Calmettes, Marseille F-13009, France. Equipe labellisée Ligue 2014.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Churikov
authors.affiliation: Cancer Research Center of Marseille (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University (AMU), Institut Paoli-Calmettes, Marseille F-13009, France. Equipe labellisée Ligue 2014.
authors.forename: Vincent
authors.initials: V
authors.lastname: Géli
authors.affiliation: Cancer Research Center of Marseille (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University (AMU), Institut Paoli-Calmettes, Marseille F-13009, France. Equipe labellisée Ligue 2014.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Simon
mesh_terms: D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D004277:DNA, Single-Stranded; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; D004720:Endonucleases; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases