Abstract
Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Eco1, a conserved acetyltransferase. However, due to the lack of known in vivo substrates, how Eco1 regulates cohesion is not understood. Here we report that yeast Eco1 and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues. Mutating these lysine residues to a nonacetylatable form leads to increased loss of sister chromatid cohesion and genome instability in both yeast and human. In addition, we clarified that the acetyltransferase activity of Eco1 is essential for its function. Our study thus identified a molecular target for the acetyltransferase Eco1 and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylation
-
Acetyltransferases / metabolism*
-
Amino Acid Sequence
-
Cell Cycle Proteins / chemistry
-
Cell Cycle Proteins / metabolism*
-
Cell Line
-
Cell Proliferation
-
Cell Survival
-
Chondroitin Sulfate Proteoglycans / chemistry
-
Chondroitin Sulfate Proteoglycans / metabolism*
-
Chromosomal Proteins, Non-Histone / chemistry
-
Chromosomal Proteins, Non-Histone / metabolism*
-
Genomic Instability
-
Humans
-
Lysine / metabolism
-
Molecular Sequence Data
-
Nuclear Proteins / metabolism*
-
S Phase*
-
Saccharomyces cerevisiae / cytology*
-
Saccharomyces cerevisiae / enzymology
-
Saccharomyces cerevisiae Proteins / chemistry
-
Saccharomyces cerevisiae Proteins / metabolism*
-
Sister Chromatid Exchange*
-
Substrate Specificity
Substances
-
Cell Cycle Proteins
-
Chondroitin Sulfate Proteoglycans
-
Chromosomal Proteins, Non-Histone
-
Nuclear Proteins
-
SMC3 protein, S cerevisiae
-
SMC3 protein, human
-
Saccharomyces cerevisiae Proteins
-
Acetyltransferases
-
ECO1 protein, S cerevisiae
-
ESCO1 protein, human
-
Lysine