A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase.
Cohesin complex mediates cohesion between sister chromatids, which promotes high-fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p during S phase to establish cohesion. The current model posits that this Eco1p-mediated acetylation promotes establishment by abrogating the ability of Wpl1p to destabilize cohesin binding to chromosomes. Here we present data from budding yeast that is incompatible with this Wpl1p-centric model. Two independent in vivo assays show that a wpl1∆ fails to suppress cohesion defects of eco1∆ cells. Moreover, a wpl1∆ also fails to suppress cohesion defects engendered by blocking just the essential Eco1p acetylation sites on Smc3p (K112, K113). Thus removing WPL1 inhibition is insufficient for generating cohesion without ECO1 activity. To elucidate how ECO1 promotes cohesion, we conducted a genetic screen and identified a cohesion activator mutation in the SMC3 head domain (D1189H). Smc3-D1189H partially restores cohesion in eco1∆ wpl1∆ or eco1 mutant cells but robustly restores cohesion in cells blocked for Smc3p K112 K113 acetylation. These data support two important conclusions. First, acetylation of the K112 K113 region by Eco1p promotes cohesion establishment by altering Smc3p head function independent of its ability to antagonize Wpl1p. Second, Eco1p targets other than Smc3p K112 K113 are necessary for efficient establishment.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Vincent
V
Guacci
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Jeremiah
J
Stricklin
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Michelle S
MS
Bloom
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Xuánzōng
X
Guō
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Meghna
M
Bhatter
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Douglas
D
Koshland
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002842:Chromatids / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C476199:RAD61 protein, S cerevisiae; C118076:ECO1 protein, S cerevisiae