title: S-phase checkpoint genes safeguard high-fidelity sister chromatid cohesion.
abstract: Cohesion establishment and maintenance are carried out by proteins that modify the activity of Cohesin, an essential complex that holds sister chromatids together. Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood. To identify additional cohesion components, we analyzed a ctf4Delta synthetic lethal screen performed on microarrays. We focused on a subset of ctf4Delta-interacting genes with genetic instability of their own. Our analyses revealed that 17 previously studied genes are also necessary for the maintenance of robust association of sisters in metaphase. Among these were subunits of the MRX complex, which forms a molecular structure similar to Cohesin. Further investigation indicated that the MRX complex did not contribute to metaphase cohesion independent of Cohesin, although an additional role may be contributed by XRS2. In general, results from the screen indicated a sister chromatid cohesion role for a specific subset of genes that function in DNA replication and repair. This subset is particularly enriched for genes that support the S-phase checkpoint. We suggest that these genes promote and protect a chromatin environment conducive to robust cohesion.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Ross 850, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Warren
authors.forename: D Mark
authors.initials: DM
authors.lastname: Eckley
authors.forename: Marina S
authors.initials: MS
authors.lastname: Lee
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Hanna
authors.forename: Adam
authors.initials: A
authors.lastname: Hughes
authors.forename: Brian
authors.initials: B
authors.lastname: Peyser
authors.forename: Chunfa
authors.initials: C
authors.lastname: Jie
authors.forename: Rafael
authors.initials: R
authors.lastname: Irizarry
authors.forename: Forrest A
authors.initials: FA
authors.lastname: Spencer
mesh_terms: D018797:Cell Cycle Proteins; D002842:Chromatids / Q000648:ultrastructure*; D002843:Chromatin / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone; D015825:Chromosomes, Fungal / Q000648:ultrastructure; D004260:DNA Repair; D004261:DNA Replication; D004586:Electrophoresis; D005656:Fungal Proteins; D005800:Genes, Fungal; D005838:Genotype; D008677:Metaphase; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016196:S Phase; D004718:Saccharomycetales / Q000502:physiology*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D009687:Nuclear Proteins; D000097722:Cohesins