title: Differential regulation of the anti-crossover and replication fork regression activities of Mph1 by Mte1.
abstract: We identified Mte1 (Mph1-associated telomere maintenance protein 1) as a multifunctional regulator of Saccharomyces cerevisiae Mph1, a member of the FANCM family of DNA motor proteins important for DNA replication fork repair and crossover suppression during homologous recombination. We show that Mte1 interacts with Mph1 and DNA species that resemble a DNA replication fork and the D loop formed during recombination. Biochemically, Mte1 stimulates Mph1-mediated DNA replication fork regression and branch migration in a model substrate. Consistent with this activity, genetic analysis reveals that Mte1 functions with Mph1 and the associated MHF complex in replication fork repair. Surprisingly, Mte1 antagonizes the D-loop-dissociative activity of Mph1-MHF and exerts a procrossover role in mitotic recombination. We further show that the influence of Mte1 on Mph1 activities requires its binding to Mph1 and DNA. Thus, Mte1 differentially regulates Mph1 activities to achieve distinct outcomes in recombination and replication fork repair.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Alma
authors.initials: A
authors.lastname: Papusha
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Koyi
authors.initials: K
authors.lastname: Choi
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Bonner
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
authors.forename: Hardeep
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Donnianni
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
authors.forename: Lucy
authors.initials: L
authors.lastname: Lu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA;
authors.forename: Michael
authors.initials: M
authors.lastname: Lichten
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Ira
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA;
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000502:physiology*; D004843:Epistasis, Genetic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D008938:Mitosis; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / 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: MHF; Mph1; Mte1; crossover formation; genome replication; homologous recombination