Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast.
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.
Zhang
Jinglan
J
Center for Molecular Discovery, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Shi
Xiaomin
X
Li
Yehua
Y
Kim
Beom-Jun
BJ
Jia
Junling
J
Huang
Zhiwei
Z
Yang
Tao
T
Fu
Xiaoyong
X
Jung
Sung Yun
SY
Wang
Yi
Y
Zhang
Pumin
P
Kim
Seong-Tae
ST
Pan
Xuewen
X
Qin
Jun
J
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012854:Sister Chromatid Exchange; D013379:Substrate Specificity
D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; C120372:SMC3 protein, S cerevisiae; C492318:SMC3 protein, human; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C118076:ECO1 protein, S cerevisiae; C479413:ESCO1 protein, human; D008239:Lysine