title: Uninterrupted MCM2-7 function required for DNA replication fork progression.
abstract: Little is known about the DNA helicases required for the elongation phase of eukaryotic chromosome replication. Minichromosome maintenance (MCM) protein complexes have DNA helicase activity but have only been functionally implicated in initiating DNA replication. Using an improved method for constructing conditional degron mutants, we show that depletion of MCMs after initiation irreversibly blocks the progression of replication forks in Saccharomyces cerevisiae. Like the Escherichia coli dnaB and SV40 T antigen helicases, therefore, the MCM complex is loaded at origins before initiation and is essential for elongation. Restricting MCM loading to the G(1) phase ensures that initiation and elongation occur just once per cell cycle.
authors.affiliation: Imperial Cancer Research Fund Clare Hall Laboratories, South Mimms, Hertfordshire, EN6 3LD, UK.
authors.forename: K
authors.initials: K
authors.lastname: Labib
authors.forename: J A
authors.initials: JA
authors.lastname: Tercero
authors.forename: J F
authors.initials: JF
authors.lastname: Diffley
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D015825:Chromosomes, Fungal / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D016195:G2 Phase; D008025:Ligases; D064148:Minichromosome Maintenance Complex Component 4; D064151:Minichromosome Maintenance Complex Component 6; D008938:Mitosis; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012093:Replicon; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C066066:UBR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; C069199:MCM2 protein, S cerevisiae; C092802:MCM4 protein, S cerevisiae; C491207:MCM6 protein, S cerevisiae; D064148:Minichromosome Maintenance Complex Component 4; D064151:Minichromosome Maintenance Complex Component 6; D008025:Ligases