title: Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance.
abstract: Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize at DNA damage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Sonia
authors.initials: S
authors.lastname: Silva
authors.affiliation: Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic;
authors.forename: Veronika
authors.initials: V
authors.lastname: Altmannova
authors.affiliation: Institute of Molecular Biology gGmbH (IMB), 55128 Mainz, Germany;
authors.forename: Sarah
authors.initials: S
authors.lastname: Luke-Glaser
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Henriksen
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Irene
authors.initials: I
authors.lastname: Gallina
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Chunaram
authors.initials: C
authors.lastname: Choudhary
authors.affiliation: Institute of Molecular Biology gGmbH (IMB), 55128 Mainz, Germany;
authors.forename: Brian
authors.initials: B
authors.lastname: Luke
authors.affiliation: Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic; National Centre for Biomolecular Research, Masaryk University, CZ-62500 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, CZ-656 91 Brno, Czech Republic; Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, CZ-656 91 Brno, Czech Republic;
authors.forename: Lumir
authors.initials: L
authors.lastname: Krejci
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark; Center for Chromosome Stability, Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0002-4830-5247
authors.initials: M
authors.lastname: Lisby
mesh_terms: D003434:Crossing Over, Genetic / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D059505:Telomere Homeostasis / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000609238:Mte1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C491240:MPH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases
keywords: DNA repair; Mph1; Mte1; genome integrity; homologous recombination; telomere maintenance