Cohesin's DNA exit gate is distinct from its entrance gate and is regulated by acetylation.
Sister chromatid cohesion is mediated by entrapment of sister DNAs by a tripartite ring composed of cohesin's Smc1, Smc3, and α-kleisin subunits. Cohesion requires acetylation of Smc3 by Eco1, whose role is to counteract an inhibitory (antiestablishment) activity associated with cohesin's Wapl subunit. We show that mutations abrogating antiestablishment activity also reduce turnover of cohesin on pericentric chromatin. Our results reveal a "releasing" activity inherent to cohesin complexes transiently associated with Wapl that catalyzes their dissociation from chromosomes. Fusion of Smc3's nucleotide binding domain to α-kleisin's N-terminal domain also reduces cohesin turnover within pericentric chromatin and permits establishment of Wapl-resistant cohesion in the absence of Eco1. We suggest that releasing activity opens the Smc3/α-kleisin interface, creating a DNA exit gate distinct from its proposed entry gate at the Smc1/3 interface. According to this notion, the function of Smc3 acetylation is to block its dissociation from α-kleisin. The functional implications of regulated ring opening are discussed.
University of Oxford, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.
Kok-Lung
KL
Chan
Maurici B
MB
Roig
Bin
B
Hu
Frédéric
F
Beckouët
Jean
J
Metson
Kim
K
Nasmyth
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000378:metabolism; D004261:DNA Replication; D009687:Nuclear Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C427726:PDS5 protein, S cerevisiae; C476199:RAD61 protein, S cerevisiae; C120372:SMC3 protein, S cerevisiae; C118076:ECO1 protein, S cerevisiae