title: The cullin Rtt101p promotes replication fork progression through damaged DNA and natural pause sites.
abstract: Accurate and complete DNA replication is fundamental to maintain genome integrity. While the mechanisms and underlying machinery required to duplicate bulk genomic DNA are beginning to emerge, little is known about how cells replicate through damaged areas and special chromosomal regions such as telomeres, centromeres, and highly transcribed loci . Here, we have investigated the role of the yeast cullin Rtt101p in this process. We show that rtt101Delta cells accumulate spontaneous DNA damage and exhibit a G(2)/M delay, even though they are fully proficient to detect and repair chromosome breaks. Viability of rtt101Delta mutants depends on Rrm3p, a DNA helicase involved in displacing proteinaceous complexes at programmed pause sites . Moreover, rtt101Delta cells show hyperrecombination at forks arrested at replication fork barriers (RFBs) of ribosomal DNA. Finally, rtt101Delta mutants are sensitive to fork arrest induced by DNA alkylation, but not by nucleotide depletion. We therefore propose that the cullin Rtt101p promotes fork progression through obstacles such as DNA lesions or tightly bound protein-DNA complexes via a new mechanism involving ubiquitin-conjugation.
authors.affiliation: Swiss Federal Institute of Technology Zurich (ETH), Institute of Biochemistry, ETH Hoenggerberg HPM G 10.0, Switzerland.
authors.forename: Brian
authors.initials: B
authors.lastname: Luke
authors.forename: Gwennaelle
authors.initials: G
authors.lastname: Versini
authors.forename: Malika
authors.initials: M
authors.lastname: Jaquenoud
authors.forename: Iram Waris
authors.initials: IW
authors.lastname: Zaidi
authors.forename: Thimo
authors.initials: T
authors.lastname: Kurz
authors.forename: Lionel
authors.initials: L
authors.lastname: Pintard
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D044842:Cullin Proteins / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D004271:DNA, Fungal / Q000096:biosynthesis*; D007399:Interphase / Q000502:physiology; D008741:Methyl Methanesulfonate; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
chemical_list: D044842:Cullin Proteins; D004271:DNA, Fungal; C476451:RTT101 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate