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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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. 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 one in which Scc2 replaces Pds5 and stimulates ATP hydrolysis required for loading and translocation.

Original languageEnglish (US)
Pages (from-to)1134-1148.e7
JournalMolecular Cell
Volume70
Issue number6
DOIs
StatePublished - Jun 21 2018

Fingerprint

Adenosine Triphosphatases
Adenosine Triphosphate
Chromatids
Chromosomes
Mutation
Hydrolysis
DNA
cohesins
Proteins

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Petela, N. J., Gligoris, T. G., Metson, J., Lee, B. G., Voulgaris, M., Hu, B., ... Nasmyth, K. A. (2018). Scc2 Is a Potent Activator of Cohesin's ATPase that Promotes Loading by Binding Scc1 without Pds5. Molecular Cell, 70(6), 1134-1148.e7. https://doi.org/10.1016/j.molcel.2018.05.022

Scc2 Is a Potent Activator of Cohesin's ATPase that Promotes Loading by Binding Scc1 without Pds5. / Petela, Naomi J.; Gligoris, Thomas G.; Metson, Jean; Lee, Byung Gil; Voulgaris, Menelaos; Hu, Bin; Kikuchi, Sotaro; Chapard, Christophe; Chen, Wentao; Rajendra, Eeson; Srinivisan, Madhusudhan; Yu, Hongtao; Löwe, Jan; Nasmyth, Kim A.

In: Molecular Cell, Vol. 70, No. 6, 21.06.2018, p. 1134-1148.e7.

Research output: Contribution to journalArticle

Petela, NJ, Gligoris, TG, Metson, J, Lee, BG, Voulgaris, M, Hu, B, Kikuchi, S, Chapard, C, Chen, W, Rajendra, E, Srinivisan, M, Yu, H, Löwe, J & Nasmyth, KA 2018, 'Scc2 Is a Potent Activator of Cohesin's ATPase that Promotes Loading by Binding Scc1 without Pds5', Molecular Cell, vol. 70, no. 6, pp. 1134-1148.e7. https://doi.org/10.1016/j.molcel.2018.05.022
Petela, Naomi J. ; Gligoris, Thomas G. ; Metson, Jean ; Lee, Byung Gil ; Voulgaris, Menelaos ; Hu, Bin ; Kikuchi, Sotaro ; Chapard, Christophe ; Chen, Wentao ; Rajendra, Eeson ; Srinivisan, Madhusudhan ; Yu, Hongtao ; Löwe, Jan ; Nasmyth, Kim A. / Scc2 Is a Potent Activator of Cohesin's ATPase that Promotes Loading by Binding Scc1 without Pds5. In: Molecular Cell. 2018 ; Vol. 70, No. 6. pp. 1134-1148.e7.
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