Evidence map›Paper›PMID 31729382›Full record

ArticleNature communications2019

Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.

Laura E Rosen, Joseph E Klebba, Jonathan B Asfaha, Chloe M Ghent, Melody G Campbell, Yifan Cheng, David O Morgan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  8. Nucleic Acids and Electrical Signals.Reviews of physiology, biochemistry and pharmacology · 2025
    Review
  9. Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.Cellular and molecular life sciences : CMLS · 2024
    Review
  10. Securin Regulates the Spatiotemporal Dynamics of Separase.bioRxiv : the preprint server for biology · 2023
    Article
  11. The molecular mechanisms of human separase regulation.Biochemical Society transactions · 2023
    Review
  12. Separase and Roads to Disengage Sister Chromatids during Anaphase.International journal of molecular sciences · 2023
    Review
  13. Mapping separase-mediated cleavage in situ.NAR genomics and bioinformatics · 2022
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Laura E RosenDepartment of Physiology, University of California, San Francisco, CA, 94143, USA.
Joseph E KlebbaDepartment of Physiology, University of California, San Francisco, CA, 94143, USA.
Jonathan B AsfahaDepartment of Physiology, University of California, San Francisco, CA, 94143, USA.
Chloe M GhentDepartment of Physiology, University of California, San Francisco, CA, 94143, USA.
Melody G CampbellDepartment of Biochemistry & Biophysics, University of California, San Francisco, CA, 94143, USA.ORCID http://orcid.org/0000-0003-1909-5751
Yifan ChengDepartment of Biochemistry & Biophysics, University of California, San Francisco, CA, 94143, USA.
David O MorganDepartment of Physiology, University of California, San Francisco, CA, 94143, USA. david.morgan@ucsf.edu.ORCID http://orcid.org/0000-0001-8753-4416
University of California, San Francisco · US

Funding

Regulatory Enzymes and Systems in Cell Cycle ControlR35GM118053 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DAVID Owen MORGAN · 2016 to 2026
$10.3M
NIGMS NIH HHS R35 GM118053
6 · The paper itself

Abstract

Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Using this enzyme, we identify an LPE motif on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage. Securin also contains a conserved LPE motif, and we provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif. Our results suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage.

Indexed as

Amino Acid MotifsAnaphaseCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsHumansMetaphaseSecurinSeparaseSubstrate SpecificityCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsRAD21 protein, humanSecurinSeparase

Identifiers

PMID31729382
PMCPMC6858450
OpenAlexW2988454773

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.