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PMID: 14742710 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

S-phase checkpoint genes safeguard high-fidelity sister chromatid cohesion.

Molecular biology of the cell ·Vol. 15 ·No. 4 ·2004-04-00 ·Pages 1724-35

Warren CD, Eckley DM, Lee MS, Hanna JS, Hughes A, Peyser B, Jie C, Irizarry R, Spencer FA

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.

MeSH Terms
Cell Cycle Proteins Chromatids/ultrastructure Chromatin/ultrastructure Chromosomal Proteins, Non-Histone Chromosomes, Fungal/ultrastructure DNA Repair DNA Replication Electrophoresis Fungal Proteins Genes, Fungal Genotype Metaphase Models, Genetic Mutation Nuclear Proteins/genetics Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis S Phase Saccharomycetales/physiology
Chemicals
Cell Cycle Proteins Chromatin Chromosomal Proteins, Non-Histone Fungal Proteins Nuclear Proteins cohesins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Warren Cheryl D
McKusick-Nathans Institute of Genetic Medicine, Ross 850, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Eckley D Mark
Lee Marina S
Hanna Joseph S
Hughes Adam
Peyser Brian
Jie Chunfa
Irizarry Rafael
Spencer Forrest A
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-09-0637
Published
2004-04-00
Epub
2004-00-23
Pages
1724-35
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC379270
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-09-0637 PMC Full Text View journal details
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