Eco1-Dependent Cohesin Acetylation During Establishment of Sister Chromatid Cohesion

Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward. This requires the replication fork–associated acetyl transferase Eco1, but Eco1's mechanism of action is not known. We identified spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast. An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion. A second set of eco1-1 suppressors inactivate the budding yeast ortholog of the cohesin destabilizer Wapl. Our results indicate that Eco1 modifies cohesin to stabilize sister chromatid cohesion in parallel with a cohesion establishment reaction that is in principle Eco1-independent.

[1]  S. Jentsch,et al.  PCNA controls establishment of sister chromatid cohesion during S phase. , 2006, Molecular cell.

[2]  Steven P. Gygi,et al.  A Molecular Determinant for the Establishment of Sister Chromatid Cohesion , 2008, Science.

[3]  Brian D. Peyser,et al.  S-phase checkpoint genes safeguard high-fidelity sister chromatid cohesion. , 2004, Molecular biology of the cell.

[4]  J. Rine,et al.  The boundaries of the silenced HMR domain in Saccharomyces cerevisiae. , 1999, Genes & development.

[5]  F. Uhlmann,et al.  A Model for ATP Hydrolysis-Dependent Binding of Cohesin to DNA , 2003, Current Biology.

[6]  Katsuhiko Shirahige,et al.  Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. , 2006, Molecular cell.

[7]  Kim Nasmyth,et al.  A Topological Interaction between Cohesin Rings and a Circular Minichromosome , 2005, Cell.

[8]  Trisha N Davis,et al.  In vivo analysis of cohesin architecture using FRET in the budding yeast Saccharomyces cerevisiae , 2007, The EMBO journal.

[9]  K. Nasmyth,et al.  Evidence that Loading of Cohesin Onto Chromosomes Involves Opening of Its SMC Hinge , 2006, Cell.

[10]  Maitreya J. Dunham,et al.  Genome-Wide Detection of Polymorphisms at Nucleotide Resolution with a Single DNA Microarray , 2006, Science.

[11]  K. Shirahige,et al.  Postreplicative Formation of Cohesion Is Required for Repair and Induced by a Single DNA Break , 2007, Science.

[12]  A. Deutschbauer,et al.  Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-α-associated protein Ctf4 is essential for chromatid disjunction during meiosis II , 2004, Journal of Cell Science.

[13]  Kim Nasmyth,et al.  Cohesion between sister chromatids must be established during DNA replication , 1998, Current Biology.

[14]  F. Spencer,et al.  Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion , 2001, Molecular and Cellular Biology.

[15]  D. Koshland,et al.  DNA Double-Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion Through Eco1 (Ctf7) , 2007, Science.

[16]  A. Chu,et al.  Use of a Genome-Wide Approach to Identify New Genes that Control Resistance of Saccharomyces cerevisiae to Ionizing Radiation , 2003, Radiation research.

[17]  C. K. Schmidt,et al.  Cell‐cycle regulation of cohesin stability along fission yeast chromosomes , 2008, The EMBO journal.

[18]  P. Hieter,et al.  Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery. , 1999, Genes & development.

[19]  J. Peters,et al.  Wapl Controls the Dynamic Association of Cohesin with Chromatin , 2006, Cell.

[20]  K. Nasmyth,et al.  From a single double helix to paired double helices and back. , 2004, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[21]  Mihoko Kai,et al.  Establishment and maintenance of sister chromatid cohesion in fission yeast by a unique mechanism , 2001, The EMBO journal.

[22]  S. Gygi,et al.  Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. , 2001, Molecular cell.

[23]  Kim Nasmyth,et al.  Structure and stability of cohesin's Smc1-kleisin interaction. , 2004, Molecular cell.

[24]  Grant W. Brown,et al.  Genetic Dissection of Parallel Sister-Chromatid Cohesion Pathways , 2007, Genetics.

[25]  K. Nasmyth,et al.  Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication. , 1999, Genes & development.

[26]  K. Nasmyth,et al.  ATP Hydrolysis Is Required for Cohesin's Association with Chromosomes , 2003, Current Biology.

[27]  T. Hirano,et al.  Human Wapl Is a Cohesin-Binding Protein that Promotes Sister-Chromatid Resolution in Mitotic Prophase , 2006, Current Biology.

[28]  Karl Mechtler,et al.  Eco1 Is a Novel Acetyltransferase that Can Acetylate Proteins Involved in Cohesion , 2002, Current Biology.