Scc2 Is a Potent Activator of Cohesin’s ATPase that Promotes Loading by Binding Scc1 without Pds5

Naomi J. Petela, Thomas G. Gligoris, Jean Metson, Byung-Gil Lee, Menelaos Voulgaris, Bin Hu, Sotaro Kikuchi, Christophe Chapard, Wentao Chen, Eeson Rajendra, Madhusudhan Srinivisan, Hongtao Yu, Jan Löwe, Kim A. Nasmyth* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)
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Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin’s ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin’s initial association with loading sites. Lastly, Scc2 mutations that permit loading in the absence of Scc4 increase Scc2’s association with chromosomal cohesin and reduce that of Pds5. We suggest that cohesin switches between two states: one with Pds5 bound that is unable to hydrolyze ATP efficiently but is capable of release from chromosomes and another in which Scc2 replaces Pds5 and stimulates ATP hydrolysis necessary for loading and translocation from loading sites
Original languageEnglish
Pages (from-to)1134-1148.e7
Number of pages23
JournalMolecular Cell
Issue number6
Early online date21 Jun 2018
Publication statusPublished - 21 Jun 2018
Externally publishedYes

Bibliographical note

We are grateful to Adele Marston for sharing yeast strains; Peter West for programming support; and Tatiana Wilson, Isobel Johns, and Stefanos Skylakakis
for invaluable technical assistance. We thank all members of the Nasmyth
group for valuable discussions. This work was funded by Cancer Research
UK (C573/A12386 to K.A.N.), the Wellcome Trust (107935/Z/15/Z to K.A.N.,
202062/Z/16/Z to B.H., and 202754/Z/16/Z to J.L.), the Medical Research
Council (MR/L018047/1 to K.A.N. and U105184326 to J.L.), the European
Research Council (294401 to K.A.N.), and the Welch Foundation (I-1441 to
H.Y.). H.Y. is an Investigator with the Howard Hughes Medical Institute.


  • cohesin
  • Scc2
  • Pds5
  • Scc1
  • cohesion
  • ATPase
  • loading
  • HAWKs


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