title: Regulation of Elg1 activity by phosphorylation.
abstract: ELG1 is a conserved gene with important roles in the maintenance of genome stability. Elg1's activity prevents gross chromosomal rearrangements, maintains proper telomere length regulation, helps repairing DNA damage created by a number of genotoxins and participates in sister chromatid cohesion. Elg1 is evolutionarily conserved, and its Fanconi Anemia-related mammalian ortholog (also known as ATAD5) is embryonic lethal when lost in mice and acts as a tumor suppressor in mice and humans. Elg1 encodes a protein that forms an RFC-like complex that unloads the replicative clamp, PCNA, from DNA, mainly in its SUMOylated form. We have identified 2 different regions in yeast Elg1 that undergo phosphorylation. Phosphorylation of one of them, S112, is dependent on the ATR yeast ortholog, Mec1, and probably is a direct target of this kinase. We show that phosphorylation of Elg1 is important for its role at telomeres. Mutants unable to undergo phosphorylation suppress the DNA damage sensitivity of Δrad5 mutants, defective for an error-free post-replicational bypass pathway. This indicates a role of phosphorylation in the regulation of DNA repair. Our results open the way to investigate the mechanisms by which the activity of Elg1 is regulated during DNA replication and in response to DNA damage.
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Dganit
authors.initials: D
authors.lastname: Shkedy
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Nishant
authors.initials: N
authors.lastname: Singh
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Shemesh
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Amir
authors.affiliation: b Department of Human Molecular Genetics and Biochemistry ; Sackler Faculty of Medicine; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Geiger
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Batia
authors.initials: B
authors.lastname: Liefshitz
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Harari
authors.affiliation: a Department of Molecular Microbiology and Biotechnology ; Tel Aviv University ; Ramat Aviv , Israel.
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology; D013058:Mass Spectrometry; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D016615:Telomere / Q000378:metabolism; D059505:Telomere Homeostasis
chemical_list: D002352:Carrier Proteins; C477609:Elg1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases
keywords: ATM/Tel1, ATR/Mec1, DNA damage response, DNA repair, DNA replication, telomeres