Evidence map›Paper›PMID 31747400›Full record

ArticlePLoS genetics2019

Recruitment of the Ulp2 protease to the inner kinetochore prevents its hyper-sumoylation to ensure accurate chromosome segregation.

Raymond T Suhandynata, Yun Quan, Yusheng Yang, Wei-Tsung Yuan, Claudio P Albuquerque, Huilin Zhou

Abstract read
In one paragraph

Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Multifaceted roles of SUMO in DNA metabolism.Nucleus (Austin, Tex.) · 2024
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. SUMO control of centromere homeostasis.Frontiers in cell and developmental biology · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. 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

6 authors.

Raymond T SuhandynataDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States of America.ORCID 0000-0002-4767-7639
Yun QuanDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States of America.
Yusheng YangDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States of America.
Wei-Tsung YuanDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States of America.
Claudio P AlbuquerqueDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States of America.
Huilin ZhouDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States of America.ORCID 0000-0002-1350-4430

Funding

Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
Suppression of duplication-mediated genome rearrangements by protein sumoylationR01GM116897 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHOU, HUILIN · 2015 to 2023
$2.6M
Regulation of Receptor Tyrosine KinasesR01GM065490 · NIGMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI DONOGHUE, DANIEL J · 2002 to 2005
$1.0M
Orbitrap Fusion Mass SpectrometerS10OD023498 · OD · LUDWIG INSTITUTE FOR CANCER RES LTD · PI ZHOU, HUILIN · 2017 to 2017
$600k
NCI NIH HHS T32 CA009523NIGMS NIH HHS R01 GM065490NIGMS NIH HHS R01 GM116897NIH HHS S10 OD023498
6 · The paper itself

Abstract

The kinetochore is the central molecular machine that drives chromosome segregation in all eukaryotes. Genetic studies have suggested that protein sumoylation plays a role in regulating the inner kinetochore; however, the mechanism remains elusive. Here, we show that Saccharomyces cerevisiae Ulp2, an evolutionarily conserved SUMO specific protease, contains a previously uncharacterized kinetochore-targeting motif that recruits Ulp2 to the kinetochore via the Ctf3CENP-I-Mcm16CENP-H-Mcm22CENP-K complex (CMM). Once recruited, Ulp2 selectively targets multiple subunits of the kinetochore, specifically the Constitutive Centromere-Associated Network (CCAN), via its SUMO-interacting motif (SIM). Mutations that impair the kinetochore recruitment of Ulp2 or its binding to SUMO result in an elevated rate of chromosome loss, while mutations that affect both result in a synergistic increase of chromosome loss rate, hyper-sensitivity to DNA replication stress, along with a dramatic accumulation of hyper-sumoylated CCAN. Notably, sumoylation of CCAN occurs at the kinetochore and is perturbed by DNA replication stress. These results indicate that Ulp2 utilizes its dual substrate recognition to prevent hyper-sumoylation of CCAN, ensuring accurate chromosome segregation during cell division.

Indexed as

Cell Cycle ProteinsCentromereChromosomal Proteins, Non-HistoneChromosome SegregationDNA-Binding ProteinsDNA ReplicationEndopeptidasesKinetochoresSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSumoylationCell Cycle ProteinsChromosomal Proteins, Non-HistoneCtf3 protein, S cerevisiaeDNA-Binding ProteinsEndopeptidasesMCM16 protein, S cerevisiaeMCM22 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsULP2 protein, S cerevisiae

Identifiers

PMID31747400
PMCPMC6892545

What OpenQuestion holds

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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.