Evidence map›Paper›PMID 28596481›Full record

ArticleOncotarget2017

Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells.

Roshan L Shrestha, Grace S Ahn, Mae I Staples, Kizhakke M Sathyan, Tatiana S Karpova, Daniel R Foltz, Munira A Basrai

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
31.4field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 129 citations in OpenAlex.

  1. Article
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  5. Determinants of centromeric nucleosome conformation.bioRxiv : the preprint server for biology · 2026
    Article
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  14. Preserving centromere identity: right amounts of CENP-A at the right place and time.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
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  20. Article

34 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Roshan L ShresthaGenetics Branch, CCR, NCI, NIH, Bethesda, MD, USA.
Grace S AhnGenetics Branch, CCR, NCI, NIH, Bethesda, MD, USA.
Mae I StaplesGenetics Branch, CCR, NCI, NIH, Bethesda, MD, USA.
Kizhakke M SathyanBiochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
Tatiana S KarpovaLaboratory of Receptor Biology and Gene Expression, CCR, NCI, NIH, Bethesda, MD, USA.
Daniel R FoltzDepartment of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL, USA.
Munira A BasraiGenetics Branch, CCR, NCI, NIH, Bethesda, MD, USA.
Center for Cancer Research · USNorthwestern University · USUniversity of Virginia · US

Funding

Molecular Determinants of Chromosome Transmission and Cell Cycle RegulationZIABC010822 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BASRAI, MUNIRA · 2009 to 2025
$29.2M
LRBGE Optical Microscopy CoreZICBC011574 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KARPOVA, TATIANA · 2014 to 2025
$7.4M
Assembly and epigenetic inheritance of the human centromereR01GM111907 · NIGMS · UNIVERSITY OF VIRGINIA · PI FOLTZ, DANIEL RICHARD · 2014 to 2022
$2.8M
NIGMS NIH HHS R01 GM111907
6 · The paper itself

Abstract

Chromosomal instability (CIN) is a hallmark of many cancers and a major contributor to tumorigenesis. Centromere and kinetochore associated proteins such as the evolutionarily conserved centromeric histone H3 variant CENP-A, associate with centromeric DNA for centromere function and chromosomal stability. Stringent regulation of cellular CENP-A levels prevents its mislocalization in yeast and flies to maintain genome stability. CENP-A overexpression and mislocalization are observed in several cancers and reported to be associated with increased invasiveness and poor prognosis. We examined whether there is a direct relationship between mislocalization of overexpressed CENP-A and CIN using HeLa and chromosomally stable diploid RPE1 cell lines as model systems. Our results show that mislocalization of overexpressed CENP-A to chromosome arms leads to chromosome congression defects, lagging chromosomes, micronuclei formation and a delay in mitotic exit. CENP-A overexpressing cells showed altered localization of centromere and kinetochore associated proteins such as CENP-C, CENP-T and Nuf2 leading to weakened native kinetochores as shown by reduced interkinetochore distance and CIN. Importantly, our results show that mislocalization of CENP-A to chromosome arms is one of the major contributors for CIN as depletion of histone chaperone DAXX prevents CENP-A mislocalization and rescues the reduced interkinetochore distance and CIN phenotype in CENP-A overexpressing cells. In summary, our results establish that CENP-A overexpression and mislocalization result in a CIN phenotype in human cells. This study provides insights into how overexpression of CENP-A may contribute to CIN in cancers and underscore the importance of understanding the pathways that prevent CENP-A mislocalization for genome stability.

Indexed as

Chromosomal InstabilityCell LineCentromereCentromere Protein AChromosome SegregationDiploidyGene ExpressionHeLa CellsHistonesHumansKinetochoresMicronuclei, Chromosome-DefectiveModels, BiologicalNeoplasmsPhenotypeProtein BindingCentromere Protein AHistonescancerCENP-Acentromereschromosomal instabilityChromosome SectionDAXX

Identifiers

PMID28596481
PMCPMC5564523
OpenAlexW2618563542

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.