DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1. 2003

Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
University of Geneva, Department of Molecular Biology, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland.

To ensure proper replication and segregation of the genome, eukaryotic cells have evolved surveillance systems that monitor and react to impaired replication fork progression. In budding yeast, the intra-S phase checkpoint responds to stalled replication forks by downregulating late-firing origins, preventing spindle elongation and allowing efficient resumption of DNA synthesis after recovery from stress. Mutations in this pathway lead to high levels of genomic instability, particularly in the presence of DNA damage. Here we demonstrate by chromatin immunoprecipitation that when yeast replication forks stall due to hydroxyurea (HU) treatment, DNA polymerases alpha and epsilon are stabilized for 40-60 min. This requires the activities of Sgs1, a member of the RecQ family of DNA helicases, and the ATM-related kinase Mec1, but not Rad53 activation. A model is proposed whereby Sgs1 helicase resolves aberrantly paired structures at stalled forks to maintain single-stranded DNA that allows RP-A and Mec1 to promote DNA polymerase association.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D004259 DNA-Directed DNA Polymerase DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair. DNA Polymerase,DNA Polymerases,DNA-Dependent DNA Polymerases,DNA Polymerase N3,DNA Dependent DNA Polymerases,DNA Directed DNA Polymerase,DNA Polymerase, DNA-Directed,DNA Polymerases, DNA-Dependent,Polymerase N3, DNA,Polymerase, DNA,Polymerase, DNA-Directed DNA,Polymerases, DNA,Polymerases, DNA-Dependent DNA
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004265 DNA Helicases Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition, DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands. ATP-Dependent DNA Helicase,DNA Helicase,DNA Unwinding Protein,DNA Unwinding Proteins,ATP-Dependent DNA Helicases,DNA Helicase A,DNA Helicase E,DNA Helicase II,DNA Helicase III,ATP Dependent DNA Helicase,ATP Dependent DNA Helicases,DNA Helicase, ATP-Dependent,DNA Helicases, ATP-Dependent,Helicase, ATP-Dependent DNA,Helicase, DNA,Helicases, ATP-Dependent DNA,Helicases, DNA,Protein, DNA Unwinding,Unwinding Protein, DNA,Unwinding Proteins, DNA
D004271 DNA, Fungal Deoxyribonucleic acid that makes up the genetic material of fungi. Fungal DNA
D006918 Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Hydroxycarbamid,Hydrea,Oncocarbide
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D016196 S Phase Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome. S Period,Period, S,Periods, S,Phase, S,Phases, S,S Periods,S Phases

Related Publications

Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
August 2004, Genes & development,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
March 2016, Scientific reports,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
May 2021, The journal of physical chemistry. B,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
February 2005, Genes & development,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
October 2009, Genes & development,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
October 2009, Genes & development,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
October 2009, Nucleic acids research,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
October 2016, Methods (San Diego, Calif.),
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
July 2013, The EMBO journal,
Jennifer A Cobb, and Lotte Bjergbaek, and Kenji Shimada, and Christian Frei, and Susan M Gasser
December 2003, Genes & development,
Copied contents to your clipboard!