Evidence map›Paper›PMID 38600242›Full record

ArticleThe EMBO journal2024

DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains.

Vinutha Balachandra, Roshan L Shrestha, Colin M Hammond, Shinjen Lin, Ivo A Hendriks, Subhash Chandra Sethi, Lu Chen, Samantha Sevilla, Natasha J Caplen, Raj Chari and 8 more

Abstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

18 authors.

Vinutha BalachandraYeast Genome Stability Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Roshan L ShresthaYeast Genome Stability Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Colin M HammondNovo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. colin.hammond@liverpool.ac.uk.ORCID http://orcid.org/0000-0003-0571-5710
Shinjen LinFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
Ivo A HendriksNovo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-1439-3701
Subhash Chandra SethiYeast Genome Stability Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lu ChenFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
Samantha SevillaCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8734-9875
Natasha J CaplenFunctional Genetics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Raj ChariGenome Modification Core (GMC), Frederick National Lab for Cancer Research, Frederick, MD, USA.ORCID http://orcid.org/0000-0002-2216-313X
Tatiana S KarpovaOptical Microscopy Core, Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-6025-2128
Katherine McKinnonFlow Cytometry Core, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Matthew Am ToddNovo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-1587-3571
Vishal KopardeCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8978-8495
Ken Chih-Chien ChengFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
Michael L NielsenNovo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Anja GrothNovo Nordisk Foundation Center for Protein Research (CPR), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Munira A BasraiYeast Genome Stability Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. basraim@nih.gov.ORCID http://orcid.org/0000-0003-0628-8052

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
CCR Collaborative Bioinformatics ResourceZICBC011532 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MALIK, MARIAM · 2013 to 2025
$33.7M
Molecular Determinants of Chromosome Transmission and Cell Cycle RegulationZIABC010822 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BASRAI, MUNIRA · 2009 to 2025
$29.2M
Discovery of genes required for expression or activity of fusion oncogenesZIABC011704 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CAPLEN, NATASHA · 2016 to 2025
$15.8M
CCR VB FACS COREZICBC010936 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MCKINNON, KATHERINE · 2009 to 2025
$10.9M
Trans-NIH RNAi Facility (TNRF)ZICTR000041 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI CHENG, KEN · 2015 to 2025
$9.4M
LRBGE Optical Microscopy CoreZICBC011574 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KARPOVA, TATIANA · 2014 to 2025
$7.4M
European Research Council, Lund-beck Foundation, Independent Research Fund Denmark, Novo Nordisk Foundation ERC CoG 724436,R198-2015-269 and R313-2019-448,7016-00042B,NNF21OC0067425,NNF14CC0001HHS | NIH | NCI | Center for Cancer Research (CCR) ZIA BC 010822HHS | NIH | NCI | Center for Cancer Research (CCR) ZIA BC 011704Independent Research Fund Denmark, European Union's Horizon 2020 research and innovation program, Danish Cancer Society 0135-00096B and 8020-00220B,EPIC-XS-823839,R146-A9159-16-S2NCI NIH HHS 75N91019D00024NCI NIH HHS HHSN261201500003I
6 · The paper itself

Abstract

The centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen for regulators of CENP-A localization which identified DNAJC9, a J-domain protein implicated in histone H3-H4 protein folding, as a factor restricting CENP-A mislocalization. Cells lacking DNAJC9 exhibit mislocalization of CENP-A throughout the genome, and CIN phenotypes. Global interactome analysis showed that DNAJC9 depletion promotes the interaction of CENP-A with the DNA-replication-associated histone chaperone MCM2. CENP-A mislocalization upon DNAJC9 depletion was dependent on MCM2, defining MCM2 as a driver of CENP-A deposition at ectopic sites when H3-H4 supply chains are disrupted. Cells depleted for histone H3.3, also exhibit CENP-A mislocalization. In summary, we have defined novel factors that prevent mislocalization of CENP-A, and demonstrated that the integrity of H3-H4 supply chains regulated by histone chaperones such as DNAJC9 restrict CENP-A mislocalization and CIN.

Indexed as

Centromere Protein AChromosomal InstabilityHistonesCentromereChromosomal Proteins, Non-HistoneHeLa CellsHSP40 Heat-Shock ProteinsHumansMinichromosome Maintenance Complex Component 2CENPA protein, humanCentromere Protein AChromosomal Proteins, Non-HistoneHistonesHSP40 Heat-Shock ProteinsMCM2 protein, humanMinichromosome Maintenance Complex Component 2CENP-AChromosomal instabilityDNAJC9Histone chaperone

Identifiers

PMID38600242
PMCPMC11148058

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Registered trials

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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.